91 research outputs found

    Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death

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    CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01). Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8) (p = 0.01) and had fewer multifocal tumors at PND28 (p = 0.016), compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003). In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers), while proliferation in vivo remained unaffected (p = 0.121). Activated caspase-3 was significantly decreased and β-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death

    Lignin deconstruction by anaerobic fungi

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    Lignocellulose forms plant cell walls, and its three constituent polymers, cellulose, hemicellulose and lignin, represent the largest renewable organic carbon pool in the terrestrial biosphere. Insights into biological lignocellulose deconstruction inform understandings of global carbon sequestration dynamics and provide inspiration for biotechnologies seeking to address the current climate crisis by producing renewable chemicals from plant biomass. Organisms in diverse environments disassemble lignocellulose, and carbohydrate degradation processes are well defined, but biological lignin deconstruction is described only in aerobic systems. It is currently unclear whether anaerobic lignin deconstruction is impossible because of biochemical constraints or, alternatively, has not yet been measured. We applied whole cell-wall nuclear magnetic resonance, gel-permeation chromatography and transcriptome sequencing to interrogate the apparent paradox that anaerobic fungi (Neocallimastigomycetes), well-documented lignocellulose degradation specialists, are unable to modify lignin. We find that Neocallimastigomycetes anaerobically break chemical bonds in grass and hardwood lignins, and we further associate upregulated gene products with the observed lignocellulose deconstruction. These findings alter perceptions of lignin deconstruction by anaerobes and provide opportunities to advance decarbonization biotechnologies that depend on depolymerizing lignocellulose

    Rare-gas insertion compounds of perfluorobenzene: Aromaticity of some unstable species

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    Calculations on the novel argon insertion compounds C6 F6 Arn, n=1-6, where the argon atoms are inserted into the C-F bonds in perfluorobenzene, suggest that all possible species, with one to six inserted argon atoms, occupy minima on their respective potential energy surfaces. Ring-current plots using the ipsocentric model indicate that there is no disruption of the aromatic π system upon argon insertion, and consequently all insertion compounds are aromatic according to the magnetic criterion. The barrier height for decomposition of the single-insertion compound, C6 F6 Ar, into C6 F6 +Ar is 19.5 kcalmol at HF6-311 G** and 29.5 kcalmol at B3LYP6-311 G**, suggesting that, although clearly thermodynamically unstable, argon-perfluorobenzene insertion compounds may be stable kinetically. Preliminary calculations indicate that other rare gas-perfluorobenzene insertion compounds may also be metastable. Both C6 F6 Ne and C6 F6 He are predicted to occupy minima on their respective potential energy surfaces. © 2005 American Institute of Physics

    Analyses of PACTEL passive safety injection experiments with APROS, CATHARE and RELAP5 codes

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    The European Commission fourth framework programme project ‘Assessment of passive safety injection systems of advanced light water reactors’ involved experiments on the PACTEL test facility and computer simulations of selected experiments. The experiments focused on the performance of passive safety injection systems (PSIS) of advanced light water reactors (ALWRs) in small break loss-of-coolant accident (SBLOCA) conditions. The PSIS consisted of a core make-up tank (CMT) and two pipelines. A pressure balancing line (PBL) connected the CMT to one cold leg. The injection line (IL) connected it to the downcomer. The project involved 15 experiments in three series. The experiments provided information about condensation and heat transfer processes in the CMT, thermal stratification of water in the CMT, and natural circulation flow through the PSIS lines. The project included validation of three thermal-hydraulic computer codes (APROS, CATHARE and RELAP5). The analyses showed the codes are capable of simulating the overall behaviour of the transients. The codes predicted accurately the core heatup, which occurred when the primary coolant inventory was reduced so much that the core top became free of water. The detailed analyses of the calculation results showed that some models in the codes still need improvements. Especially, further development of models for thermal stratification, condensation and natural circulation flow with small driving forces would be necessary for accurate simulation of the phenomena in the PSIS

    Interstitial deletion of the long arm of chromosome 18, del(18)(q12.2q21.1): a report of three cases of an autosomal deletion with a mild phenotype.

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    We describe three unrelated patients with apparently identical interstitial deletions of the segment (18) (q12.2q21.1). They were a short and markedly mentally retarded 5 year old girl, a macrocephalic and obese 2 1/2 year old boy with moderate mental retardation, and a macrocephalic, severely mentally retarded 5 year old boy. Findings common to all five liveborn patients so far identified as carrying this deletion include a pattern of minor dysmorphic features (prominent forehead, ptosis of the upper eyelids, full periorbital tissue, epicanthic folds, strabismus), muscular hypotonia, seizures, behavioural disorders, and lack of major malformations
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