Expression of αvβ6integrin in oral leukoplakia

The distribution of αvβ6integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β1, β3, β4, β5, fibronectin and tenascin were also studied. The integrin αvβ6was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. αvβ6integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β4at the cell surface facing the basement membrane of all specimens. The integrins β3and β5were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both αvβ6-positive and αvβ6-negative tissues. A group of 28 leukoplakia patients were followed 1–4 years after first diagnosis. In this group, initially αvβ6integrin-positive leukoplakia specimens had high tendency for disease progression while αvβ6-negative specimens did not progress. These results suggest that the expression of αvβ6integrin could be associated in the malignant transformation of oral leukoplakias. © 2000 Cancer Research Campaig

Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological malignancies characterized by a hypercellular bone marrow and a tendency to develop thrombotic complications and to evolve to myelofibrosis and acute leukemia. Unlike chronic myelogenous leukemia, where a single disease-initiating genetic event has been identified, a more complicated series of genetic mutations appear to be responsible for the BCR-ABL1-negative MPNs which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have revealed a number of epigenetic alterations that also likely contribute to disease pathogenesis and determine clinical outcome. Increasing evidence indicates that alterations in DNA methylation, histone modification, and microRNA expression patterns can collectively influence gene expression and potentially contribute to MPN pathogenesis. Examples include mutations in genes encoding proteins that modify chromatin structure (EZH2, ASXL1, IDH1/2, JAK2V617F, and IKZF1) as well as epigenetic modification of genes critical for cell proliferation and survival (suppressors of cytokine signaling, polycythemia rubra vera-1, CXC chemokine receptor 4, and histone deacetylase (HDAC)). These epigenetic lesions serve as novel targets for experimental therapeutic interventions. Clinical trials are currently underway evaluating HDAC inhibitors and DNA methyltransferase inhibitors for the treatment of patients with MPNs

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

BACKGROUND: A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. PRESENTATION OF THE HYPOTHESIS: Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. TESTING THE HYPOTHESIS: Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments

Analysis of paediatric visual acuity using Bayesian copula models with sinh-arcsinh marginal densities

We analyse paediatric ophthalmic data from a large sample of children aged between 3 and 8 years. We modify the Bayesian additive conditional bivariate copula regression model of Klein and Kneib [1] by using sinh-arcsinh marginal densities with location, scale and shape parameters that depend smoothly on a covariate. We perform Bayesian inference about the unknown quantities of our model using a specially tailored Markov chain Monte Carlo algorithm. We gain new insights about the processes which determine transformations in visual acuity with respect to age, including the nature of joint changes in both eyes as modelled with the age-related copula dependence parameter. We analyse posterior predictive distributions to identify children with unusual sight characteristics, distinguishing those who are bivariate, but not univariate outliers. In this way we provide an innovative tool that enables clinicians to identify children with unusual sight who may otherwise be missed. We compare our simultaneous Bayesian method with the two-step frequentist generalized additive modelling approach of Vatter and Chavez-Demoulin [2]

ICAR: endoscopic skull‐base surgery

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Body Size Distribution of the Dinosaurs

The distribution of species body size is critically important for determining resource use within a group or clade. It is widely known that non-avian dinosaurs were the largest creatures to roam the Earth. There is, however, little understanding of how maximum species body size was distributed among the dinosaurs. Do they share a similar distribution to modern day vertebrate groups in spite of their large size, or did they exhibit fundamentally different distributions due to unique evolutionary pressures and adaptations? Here, we address this question by comparing the distribution of maximum species body size for dinosaurs to an extensive set of extant and extinct vertebrate groups. We also examine the body size distribution of dinosaurs by various sub-groups, time periods and formations. We find that dinosaurs exhibit a strong skew towards larger species, in direct contrast to modern day vertebrates. This pattern is not solely an artefact of bias in the fossil record, as demonstrated by contrasting distributions in two major extinct groups and supports the hypothesis that dinosaurs exhibited a fundamentally different life history strategy to other terrestrial vertebrates. A disparity in the size distribution of the herbivorous Ornithischia and Sauropodomorpha and the largely carnivorous Theropoda suggests that this pattern may have been a product of a divergence in evolutionary strategies: herbivorous dinosaurs rapidly evolved large size to escape predation by carnivores and maximise digestive efficiency; carnivores had sufficient resources among juvenile dinosaurs and non-dinosaurian prey to achieve optimal success at smaller body size. © 2012 O'Gorman, Hone

Photometric and Spectroscopic Properties of Type Ia Supernova 2018oh with Early Excess Emission from the Kepler 2 Observations

Supernova (SN) 2018oh (ASASSN-18bt) is the first spectroscopically confirmed Type Ia supernova (SN Ia) observed in the Kepler field. The Kepler data revealed an excess emission in its early light curve, allowing us to place interesting constraints on its progenitor system. Here we present extensive optical, ultraviolet, and near-infrared photometry, as well as dense sampling of optical spectra, for this object. SN 2018oh is relatively normal in its photometric evolution, with a rise time of 18.3 ± 0.3 days and Δm 15(B) = 0.96 ± 0.03 mag, but it seems to have bluer B − V colors. We construct the "UVOIR" bolometric light curve having a peak luminosity of 1.49 × 1043 erg s−1, from which we derive a nickel mass as 0.55 ± 0.04 M ⊙ by fitting radiation diffusion models powered by centrally located 56Ni. Note that the moment when nickel-powered luminosity starts to emerge is +3.85 days after the first light in the Kepler data, suggesting other origins of the early-time emission, e.g., mixing of 56Ni to outer layers of the ejecta or interaction between the ejecta and nearby circumstellar material or a nondegenerate companion star. The spectral evolution of SN 2018oh is similar to that of a normal SN Ia but is characterized by prominent and persistent carbon absorption features. The C ii features can be detected from the early phases to about 3 weeks after the maximum light, representing the latest detection of carbon ever recorded in an SN Ia. This indicates that a considerable amount of unburned carbon exists in the ejecta of SN 2018oh and may mix into deeper layers