169 research outputs found

    Survival of branching random walks in random environment

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    We study survival of nearest-neighbour branching random walks in random environment (BRWRE) on Z{\mathbb Z}. A priori there are three different regimes of survival: global survival, local survival, and strong local survival. We show that local and strong local survival regimes coincide for BRWRE and that they can be characterized with the spectral radius of the first moment matrix of the process. These results are generalizations of the classification of BRWRE in recurrent and transient regimes. Our main result is a characterization of global survival that is given in terms of Lyapunov exponents of an infinite product of i.i.d. 2×22\times 2 random matrices.Comment: 17 pages; to appear in Journal of Theoretical Probabilit

    Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription

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    Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation

    DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers

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    Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligomeric complexes that bind to arrays of PRH binding sites with high affinity and specificity. We have also shown that many PRH target genes contain suitably spaced arrays of PRH sites that allow this protein to bind and regulate transcription. Here, we use analytical ultracentrifugation and electron microscopy to further characterize PRH oligomers. We use the same techniques to show that PRH oligomers bound to long DNA fragments self-associate to form highly ordered assemblies. Electron microscopy and linear dichroism reveal that PRH oligomers can form protein–DNA fibres and that PRH is able to compact DNA in the absence of other proteins. Finally, we show that DNA compaction is not sufficient for the repression of PRH target genes in cells. We conclude that DNA compaction is a consequence of the binding of large PRH oligomers to arrays of binding sites and that PRH is functionally and structurally related to the Lrp/AsnC family of proteins from bacteria and archaea, a group of proteins formerly thought to be without eukaryotic equivalents

    DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers

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    Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligomeric complexes that bind to arrays of PRH binding sites with high affinity and specificity. We have also shown that many PRH target genes contain suitably spaced arrays of PRH sites that allow this protein to bind and regulate transcription. Here, we use analytical ultracentrifugation and electron microscopy to further characterize PRH oligomers. We use the same techniques to show that PRH oligomers bound to long DNA fragments self-associate to form highly ordered assemblies. Electron microscopy and linear dichroism reveal that PRH oligomers can form protein–DNA fibres and that PRH is able to compact DNA in the absence of other proteins. Finally, we show that DNA compaction is not sufficient for the repression of PRH target genes in cells. We conclude that DNA compaction is a consequence of the binding of large PRH oligomers to arrays of binding sites and that PRH is functionally and structurally related to the Lrp/AsnC family of proteins from bacteria and archaea, a group of proteins formerly thought to be without eukaryotic equivalents

    Evaporation from three water bodies of different sizes and climates: Measurements and scaling analysis

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    Evaporation from small reservoirs, wetlands, and lakes continues to be a theoretical and practical problem in surface hydrology and micrometeorology because atmospheric flows above such systems can rarely be approximated as stationary and planar-homogeneous with no mean subsidence (hereafter referred to as idealized flow state). Here, the turbulence statistics of temperature(T)and water vapor (q)most pertinent to lake evaporation measurementsover three water bodies differing in climate, thermal inertia and degree of advective conditions are explored. The three systems included Lac Le´man in Switzerland (high thermal inertia, near homogeneous conditions with no appreciable advection due to long upwind fetch), Eshkol reservoir in Israel (intermediate thermal inertia, frequent strong advective conditions) and Tilopozo wetland in Chile (low thermal inertia, frequent but moderate advection). The data analysis focused on how similarity constants for the flux-variance approach, CT/Cq, and relative transport efficiencies RwT/Rwq, are perturbed from unity with increased advection or the active role of temperature. When advection is small and thermal inertia is large, CT/Cq 1)primarily due to the active role of temperature, which is consistent with a large number of studies conducted over bare soil and vegetated surfaces. However, when advection is significantly large, then CT/Cq >1 (orRwT/Rwq < 1). When advection is moderate and thermal inertia is low, then CT/Cq �1. This latter equality, while consistent with Monin–Obukhov similarity theory (MOST), is due to the fact that advection tends to increase CT/Cq above unity while the active role of temperature tends to decrease CT/Cq below unity. A simplified scaling analysis derived from the scalar variance budget equation, explained qualitatively how advection could per¬turb MOST scaling (assumed to represent the idealized flow state)

    Evaporation from a small water reservoir: Direct measurements and estimates

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    Summary Knowing the rate of evaporation from surface water resources such as chan¬nels and reservoirs is essential for precise management of the water balance. However, evaporation is difficult to measure experimentally over water surfaces and several tech¬niques and models have been suggested and used in the past for its determination. In this research, evaporation from a small water reservoir in northern Israel was measured and estimated using several experimental techniques and models during the rainless summer. Evaporation was measured with an eddy covariance (EC) system consisting of a three-dimensional sonic anemometer and a Krypton hygrometer. Measurements of net radia¬tion, air temperature and humidity, and water temperature enabled estimation of other energy balance components. Several models and energy balance closure were evaluated. In addition, evaporation from a class-A pan was measured at the site. EC evaporation measurements for 21 days averaged 5.48 mm day�1. Best model predictions were obtained with two combined flux-gradient and energy balance models (Penman–Mon¬teith–Unsworth and Penman–Brutsaert), which with the water heat flux term, gave sim¬ilar daily average evaporation rates, that were up to 3% smaller than the corresponding EC values. The ratio between daily pan and EC evaporation varied from 0.96 to 1.94. The bulk mass transfer coefficient was estimated using a model based on measurements of water surface temperature, evaporation rate and absolute humidity at 0.9 and 2.9 m above the water surface, and using two theoretical approaches. The bulk transfer coefficient

    Candida albicans repetitive elements display epigenetic diversity and plasticity

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    Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation

    The Value of Information for Populations in Varying Environments

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    The notion of information pervades informal descriptions of biological systems, but formal treatments face the problem of defining a quantitative measure of information rooted in a concept of fitness, which is itself an elusive notion. Here, we present a model of population dynamics where this problem is amenable to a mathematical analysis. In the limit where any information about future environmental variations is common to the members of the population, our model is equivalent to known models of financial investment. In this case, the population can be interpreted as a portfolio of financial assets and previous analyses have shown that a key quantity of Shannon's communication theory, the mutual information, sets a fundamental limit on the value of information. We show that this bound can be violated when accounting for features that are irrelevant in finance but inherent to biological systems, such as the stochasticity present at the individual level. This leads us to generalize the measures of uncertainty and information usually encountered in information theory

    Dried Blood Spheroids for Dry-State Room Temperature Stabilization of Microliter Blood Samples

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    It is well-known that 2D dried blood spots on paper offer a facile sample collection, storage, and transportation of blood. However, large volume requirements, possible analyte instability, and difficult sample recovery plague this method, lowering confidence in analyte quantification. For the first time, we demonstrate a new approach using 3D dried blood spheroids for stabilization of small volume blood samples, mitigating these effects without cold storage. Blood spheroids form on hydrophobic paper, preventing interaction between the sample and paper substrate, eliminating all chromatographic effects. Stability of the enzyme alanine transaminase and labile organic compounds such as cocaine and diazepam were also shown to increase in the spheroid by providing a critical radius of insulation. On-surface analysis of the dried blood spheroids using paper spray mass spectrometry resulted in sub-ng/mL limits of detection for all illicit drugs tested, representing 1 order of magnitude improvement compared with analysis from 2D dried blood spots

    Interphase Nucleo-Cytoplasmic Shuttling and Localization of SIRT2 during Mitosis

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    The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase. Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. We identified a functional, leptomycin B-sensitive, nuclear export signal sequence within SIRT2. During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. Cells overexpressing wild-type or a catalytically inactive SIRT2 exhibit an increase in multinucleated cells. The findings suggest a novel mechanism of regulating SIRT2 function by nucleo-cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis
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