No evidence for tephra in Greenland from the historic eruption of Vesuvius in 79 CE: implications for geochronology and paleoclimatology

Volcanic fallout in polar ice sheets provide important opportunities to date and correlate ice-core records as well as to investigate the environmental impacts of eruptions. Only the geochemical characterization of volcanic ash (tephra) embedded in the ice strata can confirm the source of the eruption, however, and is a requisite if historical eruption ages are to be used as valid chronological checks on annual ice layer counting. Here we report the investigation of ash particles in a Greenland ice core that are associated with a volcanic sulfuric acid layer previously attributed to the 79 CE eruption of Vesuvius. Major and trace element composition of the particles indicates that the tephra does not derive from Vesuvius but most likely originates from an unidentified eruption in the Aleutian arc. Using ash dispersal modelling, we find that only an eruption large enough to include stratospheric injection is likely to account for the sizeable (24–85 μm) ash particles observed in the Greenland ice at this time. Despite its likely explosivity, this event does not appear to have triggered significant climate perturbations, unlike some other large extra-tropical eruptions. In light of a recent re-evaluation of the Greenland ice-core chronologies, our findings further challenge the previous assignation of this volcanic event to 79 CE. We highlight the need for the revised Common Era ice-core chronology to be formally accepted by the wider ice-core and climate modelling communities in order to ensure robust age linkages to precisely dated historical and paleoclimate proxy records

Functional Genomics Annotation of a Statistical Epistasis Network Associated with Bladder Cancer Susceptibility

Background: Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. Findings: To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. Conclusions: The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies

Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification of these genes would be of considerable interest.</p> <p>Results</p> <p>To begin to address this issue, microarray technology was employed to elucidate in a <it>de novo </it>fashion the global role of RIP140 in RA target gene regulation of embryonal carcinoma. Subclasses of genes were affected by RIP140 in distinct manners.</p> <p>Interestingly, approximately half of the RA-dependent genes were unaffected by RIP140. Hence, RIP140 appears to discriminate between different classes of RA target genes. In general, RIP140-dependent gene expression was consistent with RIP140 functioning to limit RA signaling and tumor cell differentiation. Few if any genes were regulated in a manner to support a role for RIP140 in "active repression". We also demonstrated that RIP140 silencing sensitizes embryonal carcinoma cells to low doses of RA.</p> <p>Conclusion</p> <p>Together the data demonstrates that RIP140 has profound effects on RA-mediated gene expression in this cancer stem cell model. The RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation and the findings suggest that RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy. We discuss these data in the context of proposed models of RIP140-mediated repression.</p

Common perinatal mental disorders and post-infancy child development in rural Ethiopia:a population-based cohort study

Objective: To investigate whether maternal common mental disorders (CMD) in the postnatal period are prospectively associated with child development at 2.5 and 3.5 years in a rural low-income African setting. Methods: This study was nested within the C-MaMiE (Child outcomes in relation to Maternal Mental health in Ethiopia) population-based cohort in Butajira, Ethiopia, and conducted from 2005 to 2006. The sample comprised of 496 women who had recently given birth to living, singleton babies with recorded birth weight measurements, who were 15 to 44 years of age, and residing in six rural sub-districts. Postnatal CMD measurements were ascertained 2 months after delivery. Language, cognitive, and motor development were obtained from the child 2.5 and 3.5 years after birth using a locally adapted version of the Bayley Scales of Infant Development (3rd Ed). Maternal CMD symptoms were measured using a locally validated WHO Self-Reporting Questionnaire. A linear mixed-effects regression model was used to analyze the relationship between postnatal CMD and child development. Results: After adjusting for confounders, there was no evidence for an association between postnatal CMD and overall child development or the cognitive sub-domain in the preschool period. There was no evidence of effect modification by levels of social support, socioeconomic status, stunting, or sex of the child. Conclusions: Previous studies from predominantly urban and peri-urban settings in middle-income countries have established a relationship between maternal CMD and child development, which contrasts with the findings from this study. The risk and protective factors for child development may differ in areas characterized by high social adversity and food insecurity. More studies are needed to investigate maternal CMD’s impact on child development in low-resource and rural areas

Creation of dense polymer brush layers by the controlled deposition of an amphiphilic responsive comb polymer

We introduce a copolymer with a comb topology that has been engineered to assemble in a brush configuration at an air-water interface. The molecule comprises a 6.1 kDa poly(methyl methacrylate) backbone with a statistical amount of poly[2-(dimethyl amino)ethyl methacrylate] polybase side chains averaging 2.43 per backbone.. Brush layers deposited with the hydrophobic PMMA backbone adsorbed to hydrophobized silicon are stable in water even when stored at pH values less than 2.0 for over 24 h. The use of a Langmuir trough allows a simple controlled deposition of the layers at a variety of grafting densities. Depth profiling of brush layers was performed using neutron reflectometry and reveals a significant shifting of the responsiveness of the layer upon changing the grafting density. The degree of swelling of the layers at a pH value of 4 (below the pK(b)) decreases as grafting density increases. Lowering the pH of the subphase during deposition causes the side chains to become charged and more hydrophilic extending to a brush-like configuration while at neutral pH the side chains lie in a "pancake" conformation at the interface. (C) 2009 Elsevier Ltd. All rights reserved

Big Tech Oligopolies, Keith Cowling, and Monopoly Capitalism

This Special Issue of the Cambridge Journal of Economics (CJE) marks and celebrates forty years since the publication of Keith Cowling’s (1982) seminal Monopoly Capitalism, which synthesised, updated, and extended the earlier work of scholars such as Steindl (1952), Baran and Sweezy (1966), Hymer (1970, 1972) and Kalecki (1971). Since the publication of Monopoly Capitalism, the critical transformative event has been the latest (fourth) technological revolution and the emergence of Big Tech companies such as Facebook, Apple, Amazon, Netflix and Google (aka FAANGs), alongside Microsoft and so-called ‘gig’ or ‘sharing economy’ firms (such as Uber, Airbnb). While initially regarded as exemplars of the dynamics of contemporary capitalism, in recent years there has been a public backlash against Big Tech, and its impact and influence within the global economy. Indeed, several commentators have raised concerns that beneath the veneer of Big Tech lies potentially insidious business models and practices that have led to a rise in corporate power and the monopolisation of markets. These criticisms, however, largely ignore the contributions of earlier scholars of monopoly capitalism. This Special Issue addresses this oversight with a series of papers re-examining and extending the work of Cowling and others in the monopoly capitalism tradition, in the specific context of Big Tech. The Introduction opens with a portrait of Keith Cowling, as a person and his scholarly contribution to the field. It then provides a critical assessment of the papers in this Special Issue. In the Epilogue, we summarise and conclude

Adhesion between oppositely-charged polyelectrolytes

The adhesion between a grafted polyelectrolyte layer (brush) and a gel of an oppositely charged polyelectrolyte has been measured as a function of applied pressure, and the interface has been traced using neutron reflectometry. The interface (in aqueous medium at pH 6) between the (polycationic) brush and the (polyanionic) gel has a limited pressure-dependence, with a small amount of deformation of the interface at the brush-gel contact. Brushes with a dry thickness of up to 13 nm exhibit weak adhesion (measured using a mechanical force tester) with an adhesive failure when the gel is detached. Thicker brushes result in the gel exhibiting cohesive failure. Reversing the geometry, whereby a polycationic brush is replaced with a polyanion and the polyanionic gel is replaced with a polycation reveals that the pH-dependence of the adhesion is moderately symmetric about pH 6, but that the maximum force required to separate the polycation gel from the polyanion brush over the range of pH is greater than that for the polycation brush and polyanion gel. The polyanion used is poly(methacrylic acid) (PMAA) and polycations of poly[2-(diethyl amino)ethyl methacrylate] (PDEAEMA) and poly[2-(dimethyl amino)ethyl methacrylate] (PDMAEMA) were used

A new method to remove hybridization bias for interspecies comparison of global gene expression profiles uncovers an association between mRNA sequence divergence and differential gene expression in Xenopus

The recent sequencing of a large number of Xenopus tropicalis expressed sequences has allowed development of a high-throughput approach to study Xenopus global RNA gene expression. We examined the global gene expression similarities and differences between the historically significant Xenopus laevis model system and the increasingly used X.tropicalis model system and assessed whether an X.tropicalis microarray platform can be used for X.laevis. These closely related species were also used to investigate a more general question: is there an association between mRNA sequence divergence and differences in gene expression levels? We carried out a comprehensive comparison of global gene expression profiles using microarrays of different tissues and developmental stages of X.laevis and X.tropicalis. We (i) show that the X.tropicalis probes provide an efficacious microarray platform for X.laevis, (ii) describe methods to compare interspecies mRNA profiles that correct differences in hybridization efficiency and (iii) show independently of hybridization bias that as mRNA sequence divergence increases between X.laevis and X.tropicalis differences in mRNA expression levels also increase

Acute Hypersensitivity of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma to Low-Dose 5-Aza Deoxycytidine Is Associated with Global DNA Damage-Associated p53 Activation, Anti-Pluripotency and DNA Demethylation

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from that induced with cisplatin in NT2/D1 cells and also uniquely downregulates genes associated with pluripotency including NANOG, SOX2, GDF3 and Myc target genes. Changes in the p53 and pluripotency signatures with 5-aza were to a large extent dependent on high levels of DNMT3B. In contrast to the majority of p53 target genes upregulated by 5-aza that did not show DNA hypomethylation, several other genes induced with 5-aza had corresponding decreases in promoter methylation. These genes include RIN1, SOX15, GPER, and TLR4 and are novel candidate tumors suppressors in TGCTs. Our studies suggest that the hypersensitivity of NT2/D1 cells to low-dose 5-aza is multifactorial and involves the combined activation of p53 targets, repression of pluripotency genes, and activation of genes repressed by DNA methylation. Low-dose 5-aza therapy may be a general strategy to treat those tumors that are sustained by cells with embryonic stem-like properties. GEO number for the microarray data: GSE42647

Trapped ions in optical lattices for probing oscillator chain models

We show that a chain of trapped ions embedded in microtraps generated by an optical lattice can be used to study oscillator models related to dry friction and energy transport. Numerical calculations with realistic experimental parameters demonstrate that both static and dynamic properties of the ion chain change significantly as the optical lattice power is varied. Finally, we lay out an experimental scheme to use the spin degree of freedom to probe the phase space structure and quantum critical behavior of the ion chain