A Refined Approach to Model Anisotropy in the Lowermost Mantle

© 2018 Institute of Physics Publishing. All rights reserved. Seismic anisotropy in the lowermost mantle has been attributed to texture development during mantle convection. This study models texture evolution in a subducting slab impinging on the core-mantle boundary. Using a 3-dimensional geodynamic model with tracers recording the deformation history, a visco-plastic self-consistent (VPSC) model for polycrystal deformation, and relying on experimentally determined slip systems, aggregate grains with volume fractions of 60% orthorhombic silicate perovskite (MgSiO3), 20% cubic calcium perovskite (CaSiO3), and 20% cubic ferropericlase ((Mg,Fe)O) were deformed plastically and developed crystal preferred orientation. Forward and reverse perovskite (Pv)-postperovskite (PPv) phase transitions were included by allowing for likely orientation variant selections. Grain orientations, P (compression) and S (shear) wave velocity pole figures were calculated for each phase as well as the aggregate. The results show that dominant (001) slip on PPv can produce strong texture and shear wave anisotropy of 0.01-3.07% with VSH >VSV which agrees with seismological observations in selected areas of the D" layer

Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites

The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not. Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites, involving a nucleosome-free region (NFR) flanked by a pronounced periodic pattern in the average nucleosome density. While the periodic pattern clearly reflects well-positioned nucleosomes, the positioning mechanism is less clear. A recent experimental study by Mavrich et al. argued that the pattern observed in S. cerevisiae is qualitatively consistent with a `barrier nucleosome model', in which the oscillatory pattern is created by the statistical positioning mechanism of Kornberg and Stryer. On the other hand, there is clear evidence for intrinsic sequence preferences of nucleosomes, and it is unclear to what extent these sequence preferences affect the observed pattern. To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome positioning data both up- and downstream from NFRs. Our analysis is based on the Tonks model of statistical physics which quantifies the interplay between the excluded-volume interaction of nucleosomes and their positional entropy. We find that although the typical patterns on the two sides of the NFR are different, they are both quantitatively described by the same physical model, with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region. These boundary conditions, which can be locally encoded into the genome sequence, significantly shape the statistical distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia

Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall Imaging Study Group and Expert Consensus Recommendations of the American Society of Neuroradiology

SUMMARY: Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease

MRI plaque imaging and its role in population-based studies

Noninvasive direct vessel wall (plaque) imaging may provide a good opportunity to study unique aspects of atherosclerotic lesions in different populations. The article published by Esposito et al. provides new insights into our understanding of diabetic atherosclerotic vascular disease by using direct plaque imaging techniques. The findings from this article call for attention to more in vivo imaging to understand the nature of high-risk atherosclerosis, especially in prospective studies in diabetic patients

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Bell Correlations and the Common Future

Reichenbach's principle states that in a causal structure, correlations of classical information can stem from a common cause in the common past or a direct influence from one of the events in correlation to the other. The difficulty of explaining Bell correlations through a mechanism in that spirit can be read as questioning either the principle or even its basis: causality. In the former case, the principle can be replaced by its quantum version, accepting as a common cause an entangled state, leaving the phenomenon as mysterious as ever on the classical level (on which, after all, it occurs). If, more radically, the causal structure is questioned in principle, closed space-time curves may become possible that, as is argued in the present note, can give rise to non-local correlations if to-be-correlated pieces of classical information meet in the common future --- which they need to if the correlation is to be detected in the first place. The result is a view resembling Brassard and Raymond-Robichaud's parallel-lives variant of Hermann's and Everett's relative-state formalism, avoiding "multiple realities."Comment: 8 pages, 5 figure

Differences in carotid arterial morphology and composition between individuals with and without obstructive coronary artery disease: A cardiovascular magnetic resonance study

Objective: We sought to determine differences with cardiovascular magnetic resonance (CMR) in the morphology and composition of the carotid arteries between individuals with angiographically-defined obstructive coronary artery disease (CAD, = 50% stenosis, cases) and those with angiographically normal coronaries (no lumen irregularities, controls). Methods and results: 191 participants (50.3% female; 50.8% CAD cases) were imaged with a multi-sequence, carotid CMR protocol at 1.5T. For each segment of the carotid, lumen area, wall area, total vessel area (lumen area + wall area), mean wall thickness and the presence or absence of calcification and lipid-rich necrotic core were recorded bilaterally. In male CAD cases compared to male controls, the distal bulb had a significantly smaller lumen area (60.0 [plus or minus] 3.1 vs. 79.7 [plus or minus] 3.2 mm[super]2, p less than 0.001) and total vessel area (99.6 [plus or minus] 4.0 vs. 119.8 [plus or minus] 4.1 mm[super]2; p less than 0.001), and larger mean wall thickness (1.25 [plus or minus] 0.03 vs. 1.11 [plus or minus] 0.03 mm; p = 0.002). Similarly, the internal carotid had a smaller lumen area (37.5 [plus or minus] 1.8 vs. 44.6 [plus or minus] 1.8 mm[super]2; p = 0.006) and smaller total vessel area (64.0 [plus or minus] 2.3 vs. 70.9 [plus or minus] 2.4 mm[super]2; p = 0.04). These metrics were not significantly different between female groups in the distal bulb and internal carotid or for either gender in the common carotid. Male CAD cases had an increased prevalence of lipid-rich necrotic core (49.0% vs. 19.6%; p = 0.003), while calcification was more prevalent in both male (46.9% vs. 17.4%; p = 0.002) and female (33.3% vs. 14.6%; p = 0.031) CAD cases compared to controls. Conclusion: Males with obstructive CAD compared to male controls had carotid bulbs and internal carotid arteries with smaller total vessel and lumen areas, and an increased prevalence of lipid-rich necrotic core. Carotid calcification was related to CAD status in both males and females. Carotid CMR identifies distinct morphological and compositional differences in the carotid arteries between individuals with and without angiographically-defined obstructive CAD.Carotid Atherosclerosis (MRI) Progression Study (CAMPS, HL076378) and Cardiovascular Research Training Program (T-32, HL07838); and the General Clinical Research Center at the Wake Forest University School of Medicine (M01 RR-07122)

Domain wall brane in squared curvature gravity

We suggest a thick braneworld model in the squared curvature gravity theory. Despite the appearance of higher order derivatives, the localization of gravity and various bulk matter fields is shown to be possible. The existence of the normalizable gravitational zero mode indicates that our four-dimensional gravity is reproduced. In order to localize the chiral fermions on the brane, two types of coupling between the fermions and the brane forming scalar is introduced. The first coupling leads us to a Schr\"odinger equation with a volcano potential, and the other a P\"oschl-Teller potential. In both cases, the zero mode exists only for the left-hand fermions. Several massive KK states of the fermions can be trapped on the brane, either as resonant states or as bound states.Comment: 18 pages, 5 figures and 1 table, references added, improved version to be published in JHE

Structural constraints revealed in consistent nucleosome positions in the genome of S. cerevisiae

<p>Abstract</p> <p>Background</p> <p>Recent advances in the field of high-throughput genomics have rendered possible the performance of genome-scale studies to define the nucleosomal landscapes of eukaryote genomes. Such analyses are aimed towards providing a better understanding of the process of nucleosome positioning, for which several models have been suggested. Nevertheless, questions regarding the sequence constraints of nucleosomal DNA and how they may have been shaped through evolution remain open. In this paper, we analyze in detail different experimental nucleosome datasets with the aim of providing a hypothesis for the emergence of nucleosome-forming sequences.</p> <p>Results</p> <p>We compared the complete sets of nucleosome positions for the budding yeast (<it>Saccharomyces cerevisiae</it>) as defined in the output of two independent experiments with the use of two different experimental techniques. We found that < 10% of the experimentally defined nucleosome positions were consistently positioned in both datasets. This subset of well-positioned nucleosomes, when compared with the bulk, was shown to have particular properties at both sequence and structural levels. Consistently positioned nucleosomes were also shown to occur preferentially in pairs of dinucleosomes, and to be surprisingly less conserved compared with their adjacent nucleosome-free linkers.</p> <p>Conclusion</p> <p>Our findings may be combined into a hypothesis for the emergence of a weak nucleosome-positioning code. According to this hypothesis, consistent nucleosomes may be partly guided by nearby nucleosome-free regions through statistical positioning. Once established, a set of well-positioned consistent nucleosomes may impose secondary constraints that further shape the structure of the underlying DNA. We were able to capture these constraints through the application of a recently introduced structural property that is related to the symmetry of DNA curvature. Furthermore, we found that both consistently positioned nucleosomes and their adjacent nucleosome-free regions show an increased tendency towards conservation of this structural feature.</p

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin