2,045 research outputs found

    Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors

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    We have examined the functional significance of the organization of pre-mRNA splicing factors in a speckled distribution in the mammalian cell nucleus. Upon microinjection into living cells of oligonucleotides or antibodies that inhibit pre-mRNA splicing in vitro, we observed major changes in the organization of splicing factors in vivo. Interchromatin granule clusters became uniform in shape, decreased in number, and increased in both size and content of splicing factors, as measured by immunofluorescence. These changes were transient and the organization of splicing factors returned to their normal distribution by 24 h following microinjection. Microinjection of these oligonucleotides or antibodies also resulted in a reduction of transcription in vivo, but the oligonucleotides did not inhibit transcription in vitro. Control oligonucleotides did not disrupt splicing or transcription in vivo. We propose that the reorganization of splicing factors we observed is the result of the inhibition of splicing in vivo

    Tumor suppressor WWOX contributes to the elimination of tumorigenic cells in drosophila melanogaster

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    WWOX is a >1Mb gene spanning FRA16D Common Chromosomal Fragile Site, a region of DNA instability in cancer. Consequently, altered WWOX levels have been observed in a wide variety of cancers. In vitro studies have identified a large number and variety of potential roles for WWOX. Although its normal role in vivo and functional contribution to cancer have not been fully defined, WWOX does have an integral role in metabolism and can suppress tumor growth. Using Drosophila melanogaster as an in vivo model system, we find that WWOX is a modulator of TNFα/Egr-mediated cell death. We found that altered levels of WWOX can modify phenotypes generated by low level ectopic expression of TNFα/Egr and this corresponds to altered levels of Caspase 3 activity. These results demonstrate an in vivo role for WWOX in promoting cell death. This form of cell death is accompanied by an increase in levels of reactive oxygen species, the regulation of which we have previously shown can also be modified by altered WWOX activity. We now hypothesise that, through regulation of reactive oxygen species, WWOX constitutes a link between alterations in cellular metabolism observed in cancer cells and their ability to evade normal cell death pathways. We have further shown that WWOX activity is required for the efficient removal of tumorigenic cells from a developing epithelial tissue. Together these results provide a molecular basis for the tumor suppressor functions of WWOX and the better prognosis observed in cancer patients with higher levels of WWOX activity. Understanding the conserved cellular pathways to which WWOX contributes provides novel possibilities for the development of therapeutic approaches to restore WWOX function in cancer.Louise V. O, Keefe, Cheng Shoou Lee, Amanda Choo, Robert I. Richard

    Acoustic Emission from crumpling paper

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    From magnetic systems to the crust of the earth, many physical systems that exibit a multiplicty of metastable states emit pulses with a broad power law distribution in energy. Digital audio recordings reveal that paper being crumpled, a system that can be easily held in hand, is such a system. Crumpling paper both using the traditional hand method and a novel cylindrical geometry uncovered a power law distribution of pulse energies spanning at least two decades: (exponent 1.3 - 1.6) Crumpling initally flat sheets into a compact ball (strong crumpling), we found little or no evidence that the energy distribution varied systematically over time or the size of the sheet. When we applied repetitive small deformations (weak crumpling) to sheets which had been previously folded along a regular grid, we found no systematic dependence on the grid spacing. Our results suggest that the pulse energy depends only weakly on the size of the paper regions responsible for sound production.Comment: 12 pages of text, 9 figures, submitted to Phys. Rev. E, additional information availible at http://www.msc.cornell.edu/~houle/crumpling

    Gas emissions, minerals, and tars associated with three coal fires, Powder River Basin, USA.

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    Ground-based surveys of three coal fires and airborne surveys of two of the fires were conducted near Sheridan, Wyoming. The fires occur in natural outcrops and in abandoned mines, all containing Paleocene-age subbituminous coals. Diffuse (carbon dioxide (CO(2)) only) and vent (CO(2), carbon monoxide (CO), methane, hydrogen sulfide (H(2)S), and elemental mercury) emission estimates were made for each of the fires. Additionally, gas samples were collected for volatile organic compound (VOC) analysis and showed a large range in variation between vents. The fires produce locally dangerous levels of CO, CO(2), H(2)S, and benzene, among other gases. At one fire in an abandoned coal mine, trends in gas and tar composition followed a change in topography. Total CO(2) fluxes for the fires from airborne, ground-based, and rate of fire advancement estimates ranged from 0.9 to 780mg/s/m(2) and are comparable to other coal fires worldwide. Samples of tar and coal-fire minerals collected from the mouth of vents provided insight into the behavior and formation of the coal fires

    Harmonising higher education and professional quality assurance processes for the assessment of learning outcomes in health

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    Maree O’Keefe, Amanda Henderson, Brian Jolly, Lindy McAllister, Louisa Remedios, Rebecca Chic

    SRTR Center‐Specific Reporting Tools: Posttransplant Outcomes

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106770/1/j.1600-6143.2006.01275.x.pd

    Threshold learning outcomes: a framework for incorporating professional accreditation and AQF standards into assessment blueprinting/mapping in healthcare disciplines

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    Maree O’Keefe, Amanda Henderson, Brian Jolly, Lindy McAllister, Louisa Remedios, Rebecca Chic

    Phylogenetic relationships of Indian caecilians (Amphibia: Gymnophiona) inferred from mitochondrial rRNA gene sequences

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    India has a diverse caecilian fauna, including representatives of three of the six currently recognized families, the Caeciliidae, Ichthyophiidae, the endemic Uraeotyphlidae, but previous molecular phylogenetic studies of caecilians have not included sequences for any Indian caecilians. Partial 12S and 16S mitochondrial gene sequences were obtained for a single representative of each of the caecilian families found in India and aligned against previously reported sequences for 13 caecilian species. The resulting alignment (16 taxa, 1200 sites, of which 288 cannot be aligned unambiguously) was analyzed using parsimony, maximum-likelihood, and distance methods. As judged by bootstrap proportions, decay indices, and leaf stabilities, well-supported relationships of the Indian caecilians are recovered from the alignment. The data (1) corroborate the hypothesis, based on morphology, that the Uraeotyphlidae and Ichthyophiidae are sister taxa, (2) recover a monophyletic Ichthyophiidae, including Indian and South East Asian representatives, and (3) place the Indian caeciliid Gegeneophis ramaswamii as the sister group of the caeciliid caecilians of the Seychelles. Rough estimates of divergence times suggest an origin of the Uraeotyphlidae and Ichthyophiidae while India was isolated from Laurasia and Africa and are most consistent with an Indian origin of these families and subsequent dispersal of ichthyophiids into South East Asia
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