| 1. |
- Imai, Y., et al.
(author)
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Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury
- 2008
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 133:2, s. 235-249
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Journal article (peer-reviewed)abstract
- Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
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| 2. |
- Mikkelsen, Tarjei S, et al.
(author)
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Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
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Journal article (peer-reviewed)abstract
- We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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| 3. |
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| 4. |
- Tol, R.S.J., et al.
(author)
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Towards successful adaptation to sea-level rise along Europe's coasts
- 2008
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In: Journal of Coastal Research. ; 24:2, s. 432-442
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Journal article (peer-reviewed)abstract
- Adaptation is defined as the planned or unplanned, reactive or anticipatory, successful or unsuccessful response of a system to a change in its environment. This paper examines the current status of adaptation to sea-level rise and climate change in the context of European coasts. Adaptation can greatly reduce the impact of sea-level rise (and other coastal changes), although it requires adjustment of coastal management policies to changing circumstances. Consequently, adaptation is a social, political, and economic process, rather than just a technical exercise, as it is often conceived. The Synthesis and Upscaling of sea-level Rise Vulnerability Assessment Studies project has shown that adaptation to sea-level rise is widely divergent among European countries. Crudely, four groups of countries were identified:1. Those that do not worry about accelerated sea-level rise and should not as their coasts are not susceptible2. Those that do not worry as they have more urgent problems3. Those that do not worry but probably should4. Those that do worry and have started to adaptAt the European Union level, while coastal management is a focus, this effort is mainly targeted at today's problems. Hence, this paper suggests the need for a concerted effort to address adaptation in coastal zones across Europe. Sharing of experience among countries would facilitate this process.
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| 5. |
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| 6. |
- Corman, ML, et al.
(author)
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Consensus conference on the stapled transanal rectal resection (STARR) for disordered defaecation
- 2006
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In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 8:2, s. 98-101
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Journal article (peer-reviewed)abstract
- An international working party was convened in Rome, Italy on 16–17 June, 2005, with the purpose of developing a consensus on the application of the circular stapling instrument to the treatment of certain rectal conditions, the so-called Stapled Transanal Rectal Resection (STARR). Since the procedure has been submitted to only limited objective analysis it was felt prudent to hold a meeting of interested individuals for the purpose of evaluating the current status and to make conclusions and recommendations concerning the applicability of this new approach.
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| 7. |
- Düringer, Caroline, et al.
(author)
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Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.
- 2009
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In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 158, s. 169-179
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Journal article (peer-reviewed)abstract
- Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations.
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| 9. |
- Kirsch, Nicole, et al.
(author)
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Molecularly imprinted polymer catalysis of a Diels-Alder reaction
- 2009
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In: Journal of Molecular Catalysis B. - : Elsevier BV. - 1381-1177 .- 1873-3158. ; 58:1-4, s. 110-117
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Journal article (peer-reviewed)abstract
- A series of synthetic polymers were designed and synthesized for enhancing the rate of the Diels-Alder cycloaddition reaction of 1,3-butadiene carbamic acid benzyl ester (11) and N,N-dimethyl acrylamide (2), to yield the corresponding endo- (3) and exo- (4) reaction products. Putative transition state analogues (TSAs) for the endo- (5) and exo- (6) reaction pathways were used as templates for the synthesis of molecularly imprinted methacrylic acid (MAA)-divinylbenzene (DVB) copolymers. The polymer system utilized was selected based upon a series of (1)H NMR studies of complex formation between template and a functional monomer analogue (K(d) (app) approximate to 70 mM, d(8)-toluene, 293 K). Batch binding studies revealed that the imprinted polymers were selective for the TSA corresponding to the template used in the polymer synthesis. Studies on the influence of the polymers on the catalysis of the reaction of 1 and 2 demonstrated a 20-fold enhancement of the rate of the reaction relative to the solution reaction. A surprising temperature dependence of the reaction of 1 and 2 in the presence of the polymers was observed, which provides support for the role of template-functional monomer complexes in the catalysis of the Diels-Alder reaction.
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