Re–Os age for the Lower–Middle Pennsylvanian Boundary and comparison with associated palynoflora

AbstractThe Betsie Shale Member is a relatively thick and continuous unit that serves as a marker bed across the central Appalachian basin, in part because it includes an organic-rich shale unit at its base that is observable in drill logs. Deposited during a marine transgression, the Betsie Shale Member has been correlated to units in both Wales and Germany and has been proposed to mark the boundary between the Lower and Middle Pennsylvanian Series within North America. This investigation assigns a new Re–Os date to the base of the Betsie and examines the palynoflora and maceral composition of the underlying Matewan coal bed in the context of that date. The Matewan coal bed contains abundant lycopsid tree spores along its base with assemblage diversity and inertinite content increasing upsection, as sulfur content and ash yield decrease. Taken together, these palynologic and organic petrographic results suggest a submerged paleomire that transitioned to an exposed peat surface. Notably, separating the lower and upper benches of the Matewan is a parting with very high sulfur content (28wt.%), perhaps representing an early marine pulse prior to the full on transgression responsible for depositing the Betsie. Results from Re–Os geochronology date the base of the Betsie at 323±7.8Ma, consistent with previously determined age constraints as well as the palynoflora assemblage presented herein. The Betsie Shale Member is also highly enriched in Re (ranging from 319.7 to 1213ng/g), with high 187Re/188Os values ranging from 3644 to 5737 likely resultant from varying redox conditions between the pore water and overlying water column during deposition and early condensing of the section

Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

Indexación: Web of Science; Scopus.Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotencyhttp://mcb.asm.org/content/36/4/61

On thin plate spline interpolation

We present a simple, PDE-based proof of the result [M. Johnson, 2001] that the error estimates of [J. Duchon, 1978] for thin plate spline interpolation can be improved by $h^{1/2}$. We illustrate that ${\mathcal H}$-matrix techniques can successfully be employed to solve very large thin plate spline interpolation problem

Genetic clustering on the hippocampal surface for genome-wide association studies

Imaging genetics aims to discover how variants in the human genome influence brain measures derived from images. Genome-wide association scans (GWAS) can screen the genome for common differences in our DNA that relate to brain measures. In small samples, GWAS has low power as individual gene effects are weak and one must also correct for multiple comparisons across the genome and the image. Here we extend recent work on genetic clustering of images, to analyze surface-based models of anatomy using GWAS. We performed spherical harmonic analysis of hippocampal surfaces, automatically extracted from brain MRI scans of 1254 subjects. We clustered hippocampal surface regions with common genetic influences by examining genetic correlations (rg) between the normalized deformation values at all pairs of surface points. Using genetic correlations to cluster surface measures, we were able to boost effect sizes for genetic associations, compared to clustering with traditional phenotypic correlations using Pearson's r

Antagonistic effects of transforming growth factor-beta on vitamin D3 enhancement of osteocalcin and osteopontin transcription: reduced interactions of vitamin D receptor/retinoid X receptor complexes with vitamin E response elements

Osteocalcin and osteopontin are noncollagenous proteins secreted by osteoblasts and regulated by a complex interplay of systemic and locally produced factors, including growth factors and steroid hormones. We investigated the mechanism by which transforming growth factor-beta (TGF beta) inhibits 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-enhanced expression of the osteocalcin (OC) and osteopontin (OP) genes. ROS 17/2.8 cells, in which both genes are expressed, were transfected with reporter constructs driven by native (i.e. wild-type) rat OC and mouse OP promoters. TGF beta abrogated the 1,25-(OH)2D3 enhanced transcription of both the OC and OP genes. The inhibitory TGF beta response for each requires vitamin D response element (VDRE) sequences, although there are additional contributions from proximal basal regulatory elements. These transcriptional effects were further investigated for contribution of the trans-activating factors, which interact with OC and OP VDREs, involving the vitamin D receptor (VDR) and retinoid X receptor (RXR). Gel mobility shift assays show that TGF beta significantly reduces induction of the heterodimers VDR/RXR complexes in 1,25-(OH)2D3-treated ROS 17/2.8 cells. However, Western blot and ligand binding analysis reveal that TGF beta does not affect nuclear availability of the VDR. We also show that activator protein-1 activity is up-regulated by TGF beta; thus, activator protein-1 binding sites in the OC promoter may potentially contribute to inhibitory effects of TGF beta on basal transcription. Our studies demonstrate that the inhibitory action of TGF beta on the 1,25-(OH)2D3 enhancement of OC and OP transcription in osteoblastic cells results from modulations of protein-DNA interactions at the OC and OP VDRE, which cannot be accounted for by changes in VDR protein levels. As OC and OP participate in bone turnover, our results provide insight into the contributions of TGF beta and 1,25-(OH)2D3 to VDR-mediated gene regulatory mechanism operative in bone formation and/or resorption events

Nonlinear porous medium flow with fractional potential pressure

We study a porous medium equation, with nonlocal diffusion effects given by an inverse fractional Laplacian operator. We pose the problem in n-dimensional space for all t>0 with bounded and compactly supported initial data, and prove existence of a weak and bounded solution that propagates with finite speed, a property that is nor shared by other fractional diffusion models.Comment: 32 pages, Late

Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a mutation or deletion of the maternally inherited UBE3A allele. In neurons, the paternally inherited UBE3A allele is silenced in cis by a long non-coding RNA called UBE3A-ATS. Here, as part of a systematic screen, we found that Cas9 can be used to activate ('unsilence') paternal Ube3a in cultured mouse and human neurons when targeted to Snord115 genes, which are small nucleolar RNAs that are clustered in the 3′ region of Ube3a-ATS. A short Cas9 variant and guide RNA that target about 75 Snord115 genes were packaged into an adeno-associated virus and administered to a mouse model of AS during the embryonic and early postnatal stages, when the therapeutic benefit of restoring Ube3a is predicted to be greatest1,2. This early treatment unsilenced paternal Ube3a throughout the brain for at least 17 months and rescued anatomical and behavioural phenotypes in AS mice. Genomic integration of the adeno-associated virus vector into Cas9 target sites caused premature termination of Ube3a-ATS at the vector-derived polyA cassette, or when integrated in the reverse orientation, by transcriptional collision with the vector-derived Cas9 transcript. Our study shows that targeted genomic integration of a gene therapy vector can restore the function of paternally inherited UBE3A throughout life, providing a path towards a disease-modifying treatment for a syndromic neurodevelopmental disorder

Charge Fluctuations on Membrane Surfaces in Water

We generalize the predictions for attractions between over-all neutral surfaces induced by charge fluctuations/correlations to non-uniform systems that include dielectric discontinuities, as is the case for mixed charged lipid membranes in an aqueous solution. We show that the induced interactions depend in a non-trivial way on the dielectric constants of membrane and water and show different scaling with distance depending on these properties. The generality of the calculations also allows us to predict under which dielectric conditions the interaction will change sign and become repulsive

Implementation and Validation of Schapery-Rand Anisotropic Viscoelasticity Model for Super-Pressure Balloons

The thin film used for the NASA Ultra Long Duration Balloons (ULDB) shows con-siderable time-dependent behaviour. Furthermore, experiments on scaled ULDB balloons have revealed that wrinkles are present over a wide range of pressures. A numerical model has been developed describing the nonlinear anisotropic viscoelastic material behaviour by means of a Schapery-type model and this model has been extended to model wrinkling by means of a user-defined subroutine in the finite-element package ABAQUS. After a description of the viscoelastic modelling approach, a lobe of a 48 gore ULDB flat facet balloon is modelled and compared to experimental results. Additionally two test cases of anisotropic wrinkling are presented, one involving a flat membrane and one a cylindrical balloon structure. I