1,981 research outputs found

    Conserved upstream open reading frames in higher plants

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    Background Upstream open reading frames (uORFs) can down-regulate the translation of the main open reading frame (mORF) through two broad mechanisms: ribosomal stalling and reducing reinitiation efficiency. In distantly related plants, such as rice and Arabidopsis, it has been found that conserved uORFs are rare in these transcriptomes with approximately 100 loci. It is unclear how prevalent conserved uORFs are in closely related plants. Results We used a homology-based approach to identify conserved uORFs in five cereals (monocots) that could potentially regulate translation. Our approach used a modified reciprocal best hit method to identify putative orthologous sequences that were then analysed by a comparative R-nomics program called uORFSCAN to find conserved uORFs. Conclusion This research identified new genes that may be controlled at the level of translation by conserved uORFs. We report that conserved uORFs are rare (<150 loci contain them) in cereal transcriptomes, are generally short (less than 100 nt), highly conserved (50% median amino acid sequence similarity), position independent in their 5'-UTRs, and their start codon context and the usage of rare codons for translation does not appear to be important.Michael K Tran, Carolyn J Schultz and Ute Bauman

    The synthetic triterpenoid CDDO-methyl ester modulates microglial activities, inhibits TNF production, and provides dopaminergic neuroprotection

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    <p>Abstract</p> <p>Background</p> <p>Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific microglial activities modulated by CDDO-Me <it>in vitro</it>, and to determine the extent to which this modulation affords neuroprotection against inflammatory stimuli.</p> <p>Methods</p> <p>We tested the synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) in various <it>in vitro </it>assays using the murine BV2 microglia cell line, mouse primary microglia, or mouse primary peritoneal macrophages to investigate its effects on proliferation, inflammatory gene expression, cytokine secretion, and phagocytosis. The antioxidant and neuroprotective effects of CDDO-Me were also investigated in primary neuron/glia cultures from rat basal forebrain or ventral midbrain.</p> <p>Results</p> <p>We found that at low nanomolar concentrations, treatment of rat primary mesencephalon neuron/glia cultures with CDDO-Me resulted in attenuated LPS-, TNF- or fibrillar amyloid beta 1–42 (Aβ1–42) peptide-induced increases in reactive microglia and inflammatory gene expression without an overall effect on cell viability. In functional assays CDDO-Me blocked death in the dopaminergic neuron-like cell line MN9D induced by conditioned media (CM) of LPS-stimulated BV2 microglia, but did not block cell death induced by addition of TNF to MN9D cells, suggesting that dopaminergic neuroprotection by CDDO-Me involved inhibition of microglial-derived cytokine production and not direct inhibition of TNF-dependent pro-apoptotic pathways. Multiplexed immunoassays of CM from LPS-stimulated microglia confirmed that CDDO-Me-treated BV2 cells produced decreased levels of specific subsets of cytokines, in particular TNF. Lastly, CDDO-Me enhanced phagocytic activity of BV2 cells in a stimulus-specific manner but inhibited generation of reactive oxygen species (ROS) in mixed neuron/glia basal forebrain cultures and dopaminergic cells.</p> <p>Conclusion</p> <p>The neuroimmune modulatory properties of CDDO-Me indicate that this potent antioxidant and anti-inflammatory compound may have therapeutic potential to modify the course of neurodegenerative diseases characterized by chronic neuroinflammation and amyloid deposition. The extent to which synthetic triterpenoids afford therapeutic benefit in animal models of Parkinson's and Alzheimer's disease deserves further investigation.</p

    Justice in the Air: Tracking Toxic Pollution from America's Industries and Companies to Add to Our States, Cities, and Neighborhoods

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    This new environmental justice study examines not only who receives the disproportionate share of toxic air releases -- low-income communities and people of color -- but who is releasing them.Justice in the Air: Tracking Toxic Pollution from America's Industries and Companies to Our States, Cities, and Neighborhoods uses the EPA's Toxic Release Inventory and Risk Screening Environmental Indicators to explore the demographics of those who are most affected by toxic pollution, and then establishes the corporate ownership of the plants responsible. Justice in the Air enhances the data available in PERI's Toxic 100 Report with a new environmental justice scorecard, ranking the Toxic 100 companies by the share of their health impacts from toxic air pollution that falls upon minority and low-income communities. The authors conclude by recommending four ways the right-to-know and environmental justice movements can use these findings in their efforts to protect the health of vulnerable communities

    Large scale structure around a z=2.1 cluster

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    The most prodigious starburst galaxies are absent in massive galaxy clusters today, but their connection with large scale environments is less clear at z≳2z\gtrsim2. We present a search of large scale structure around a galaxy cluster core at z=2.095z=2.095 using a set of spectroscopically confirmed galaxies. We find that both color-selected star-forming galaxies (SFGs) and dusty star-forming galaxies (DSFGs) show significant overdensities around the z=2.095z=2.095 cluster. A total of 8 DSFGs (including 3 X-ray luminous active galactic nuclei, AGNs) and 34 SFGs are found within a 10 arcmin radius (corresponds to ∼\sim15 cMpc at z∼2.1z\sim2.1) from the cluster center and within a redshift range of Δz=0.02\Delta z=0.02, which leads to galaxy overdensities of δDSFG∼12.3\delta_{\rm DSFG}\sim12.3 and δSFG∼2.8\delta_{\rm SFG}\sim2.8. The cluster core and the extended DSFG- and SFG-rich structure together demonstrate an active cluster formation phase, in which the cluster is accreting a significant amount of material from large scale structure while the more mature core may begin to virialize. Our finding of this DSFG-rich structure, along with a number of other protoclusters with excess DSFGs and AGNs found to date, suggest that the overdensities of these rare sources indeed trace significant mass overdensities. However, it remains puzzling how these intense star formers are triggered concurrently. Although an increased probability of galaxy interactions and/or enhanced gas supply can trigger the excess of DSFGs, our stacking analysis based on 850 μ\mum images and morphological analysis based on rest-frame optical imaging do not show such enhancements of merger fraction and gas content in this structure.Comment: 11 pages, 4 figures, ApJ accepte

    Biotransformation of an uncured composite material

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    The feasibility of biologically degrading prepreg wastes was studied. The work was conducted with the intention of obtaining baseline data that would facilitate the achievement of two long-range goals. These goals are: (1) the biological remediation of the hazardous components in the prepreg wastes, and (2) providing the potential for recycling the prepreg waste fibers. The experiments examined a prepreg that employs an bismaleimide resin system. Initial results demonstrated an obvious deterioration of the prepreg material when incubated with several bacterial strains. The most active cultures were identified as a mixture of 'Bacillus cereus' and 'Pseudomonas sp'. Gas chromatography analyses revealed seven primary compounds in the resin mixture. Biotransformation studies, using the complete prepreg material, demonstrated on obvious loss of all seven organic compounds. Gas chromatography-mass spectrometry analyses resulted in structure assignments for the two primary components of the resin. Both were analogs of Bisphenol A; one being bismaleimide, and the other being Bisphenol A containing a diglycidyl moiety. The 'diglycidyl analog' was purified using thin-layer chromatography and the biotransformation of this compound (at 27 ug/ml bacterial culture) was monitored. After a seven-day incubation, approximately 40% of the organic compound was biotransformed. These results demonstrate the biotransformation of the prepreg resin and indicate that biological remediation of the prepreg wastes is feasible

    Electrochemical Investigation of Azurin Thermodynamic and Adsorption Properties at Monolayer-Protected Cluster Film Assemblies – Evidence for a More Homogeneous Adsorption Interface

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    Thermodynamic and adsorption properties of protein monolayer electrochemistry (PME) are examined for Pseudomonas aeruginosa azurin (AZ) immobilized at an electrode modified with a networked film of monolayer-protected clusters (MPCs) to assess if nanoparticle films of this nature offer a more homogeneous adsorption interface compared to traditional self-assembled monolayer (SAM) modified electrodes. Specifically, electrochemistry is used to assess properties of surface coverage, formal potential, peak broadening, and electron transfer (ET) kinetics as a function of film thickness. The modification of a surface with dithiol-linked films of MPCs (Au225C675) provides a more uniform binding interface for AZ that results in voltammetry with less peak broadening (mV) compared to SAMs (\u3e120–130 mV). Improved homogeneity of the MPC interface for protein adsorption is confirmed by atomic force microscopy imaging that shows uniform coverage of the gold substrate topography and by electrochemical analysis of film properties during systematic desorption of AZ, which indicates a more homogeneous population of adsorbed protein at MPC films. These results suggest MPC film assemblies may be used in PME to provide greater molecular level control of the protein adsorption interface, a development with applications for strategies to study biological ET processes as well as the advancement of biosensor technologies
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