TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Stress Drop Variation of Deep‐Focus Earthquakes Based on Empirical Green’s Functions

We analyze source characteristics of global, deep‐focus (>350 km) earthquakes with moment magnitudes (Mw) larger than 6.0–8.2 using teleseismic P‐wave and S‐wave spectra and an empirical Green’s functions approach. We estimate the corner frequency assuming Brune’s source model and calculate stress drops assuming a circular crack model. Based on P‐wave and S‐wave spectra, the one standard deviation ranges are 3.5–369.8 and 8.2–328.9 MPa, respectively. Based on the P‐wave analysis, the median of our stress drop estimates is about a factor of 10 higher than the median stress drop of shallow earthquakes with the same magnitude estimated by Allmann and Shearer (2009, https://doi.org/10.1029/2008JB005821). This suggests that, on average, the shear stress of deep faults in the mantle transition zone is an order of magnitude higher than the shear stress of faults in the crust. The wide range of stress drops implies coexistence of multiple physical mechanisms.Plain Language SummaryThe change of shear stress (i.e., stress drop) during an earthquake is thought to be larger for deeper earthquakes than shallow earthquakes because of higher overburden pressure. However, the observational evidence for stress drop dependence on depth is still inconclusive. We estimate stress drops of earthquakes deeper than 400 km from recorded ground motion spectra. We find that the median stress drop of deep earthquakes is about one order of magnitude higher than the stress drop of shallow (<50 km) earthquakes. This implies that the shear stress of deep faults is moderately higher than of faults in the crust. The wide range of our stress drop estimates suggests that various mechanisms producing deep earthquakes coexist.Key PointsEmpiricalGreen’s functions are applied to analyze stress drops of deep‐focus earthquakesOne standard deviation ranges are 3.5–369.8 MPa for P waves and 8.2–328.9 MPa for S wavesThe median stress drops suggest that fault shear stress is an order of magnitude higher in the mantle than in the crustPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154937/1/grl60493_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154937/2/grl60493.pd

Evaluation of rocking and coupling rotational linear stiffness coefficients of adjacent foundations

This paper presents closed-form expressions for rocking spring stiffnesses and coupling interaction rotational spring stiffnesses for a set of closely spaced footings. Substructuring is used to derive analytically the exact reduced order spring models of the system. The stiffness coefficients of this reduced order model are determined by using (1) an extended, novel application of Boussinesq's surface displacement of a point-loaded half-space and (2) an empirically derived formulation that makes use of both finite-element and experimental results. Further validation suggests that, within the scope of epistemic uncertainty present in the physical world, the interaction formulas between two footings are sufficient for more general multifooting interaction cases.</p

Moral disengagement as a self-regulatory cognitive process of transgressions: psychometric evidence of the bandura scale in Chilean adolescents

National Research and Development Agency of Chile (Agencia Nacional de investigación y Desarrollo [ANID]) [21180734]; Direccion de investigación, Universidad de La Frontera [DIUFRO DI21-0106

Co-active coping inventory: development and validation for the Chilean population

Dirección de Investigación, Universidad de La Frontera (Chile

Zin in leven in de gloria?

Afscheidsredes PThU Kampen d.d. 4 november 2011. Bevat: L.J. van de Brom, God schept ons een zinvolle ruimte : de metafoor van de eigenzinnige tuinman (p. 3-23) en E.R. Jonker, Leren leven in de gloria : vormen, beschaven, geloven (p. 24-47)

Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

BACKGROUND: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. METHODS: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. RESULTS: We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ERα-dependent overexpression of FGFR2, whereas resistance to fulvestrant was associated with ERα-dependent isoform switching, which correlated with altered response to KGF. CONCLUSION: E2 may partly alter cellular proteome through alternative splicing uncoupled to its effects on transcription initiation and aberration in E2-induced alternative splicing events may influence response to anti-estrogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Congenital Diaphragmatic Hernia Defect Size and Infant Morbidity at Discharge

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A trifactorial model of detection of deception using thermography

[EN]Most theories of detection of deception relate lying to three factors: (1) cognitive load, (2) subjective arousal, and (3) convincing impression. The evidence suggests that a higher temperature of the forehead is related to cognitive load, and lower temperature of the nose is associated with subjective arousal, and a higher temperature of the cheeks is related to convincing impression.Here, we took into account these three factors and, at the same time, associated the thermal change in specific facial regions of interest (RIOIs) with each one of them. More importantly, we studied the combination of the thermal changes in the ROIs to establish the best combination to detect deception. Our results confirm an association between thermal changes in different ROIs and the three factor above. The best combination in the thermal changes of the ROIs for detecting deception (producind 83% accuracy and 13% false alarms in Experiment 1) is the one that was termed "at least two of the three ROIs" where there is a lower temperature of the nose and/or a higher forehead temperature. This finding constitutes an advance for detecting deception in multiple forensic contexts