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991.
Félix-Faure Jim Gaillard Jérémie Descloux Stéphane Chanudet Vincent Poirel Alain Baudoin Jean-Marc Avrillier Jean-Noël Millery Annie Dambrine Etienne 《Ecosystems》2019,22(2):312-330
Ecosystems - When a water reservoir is created, the pre-existing soils and vegetation are flooded. Here, we took advantage of the complete emptying of the Sarrans Reservoir, which was flooded... 相似文献
992.
Stéphane Sengmany Mathilde Sitter Eric Léonel Erwan Le Gall Gervaise Loirand Thierry Martens Didier Dubreuil Florian Dilasser Morgane Rousselle Vincent Sauzeau Jacques Lebreton Muriel Pipelier Rémy Le Guével 《Bioorganic & medicinal chemistry letters》2019,29(5):755-760
Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways. 相似文献
993.
SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel,CNS penetrant tricyclic M4 PAMs
Trevor C. Chopko Changho Han Alison R. Gregro Darren W. Engers Andrew S. Felts Mike S. Poslusney Katrina A. Bollinger Ryan D. Morrison Michael Bubser Atin Lamsal Vincent B. Luscombe Hyekyung P. Cho Nathalie C. Schnetz-Boutaud Alice L. Rodriguez Sichen Chang J. Scott Daniels Donald F. Stec Colleen M. Niswender Bruce J. Melancon 《Bioorganic & medicinal chemistry letters》2019,29(16):2224-2228
This letter describes progress towards an M4 PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M4 PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats. 相似文献
994.
995.
Simon Nimpf Gregory Charles Nordmann Daniel Kagerbauer Erich Pascal Malkemper Lukas Landler Artemis Papadaki-Anastasopoulou Lyubov Ushakova Andrea Wenninger-Weinzierl Maria Novatchkova Peter Vincent Thomas Lendl Martin Colombini Matthew J. Mason David Anthony Keays 《Current biology : CB》2019,29(23):4052-4059.e4
996.
Yumin Dai Ashley N. Peralta Jessica E. Wynn Chringma Sherpa Hao Li Astha Verma Stuart F.J. Le Grice Webster L. Santos 《Bioorganic & medicinal chemistry》2019,27(8):1759-1765
Interaction of HIV-1 rev response element (RRE) RNA with its cognate protein, Rev, is critical for HIV-1 replication. Understanding the mode of interaction between RRE RNA and ligands at the binding site can facilitate RNA molecular recognition as well as provide a strategy for developing anti-HIV therapeutics. Our approach utilizes branched peptides as a scaffold for multivalent binding to RRE IIB (high affinity rev binding site) with incorporation of unnatural amino acids to increase affinity via non-canonical interactions with the RNA. Previous high throughput screening of a 46,656-member library revealed several hits that bound RRE IIB RNA in the sub-micromolar range. In particular, the lead compound, 4B3, displayed a Kd value of 410?nM and demonstrated selectivity towards RRE. A ribonuclease protection assay revealed that 4B3 binds to the stem-loop structure of RRE IIB RNA, which was confirmed by SHAPE analysis with 234 nt long NL4-3 RRE RNA. Our studies further indicated interaction of 4B3 with both primary and secondary Rev binding sites. 相似文献
997.
Katie N. Kang Dustin R. Klein Misha I. Kazi Franois Gurin Vincent Cattoir Jennifer S. Brodbelt Joseph M. Boll 《Molecular microbiology》2019,111(6):1604-1616
The Enterobacter cloacae complex (ECC) consists of closely related bacteria commonly associated with the human microbiota. ECC are increasingly isolated from healthcare‐associated infections, demonstrating that these Enterobacteriaceae are emerging nosocomial pathogens. ECC can rapidly acquire multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the highly conserved lipid A component of the Gram‐negative outer membrane. Many Enterobacteriaceae fortify their outer membrane with cationic amine‐containing moieties to prevent CAMP binding, which can lead to cell lysis. The PmrAB two‐component system (TCS) directly activates 4‐amino‐4‐deoxy‐l ‐arabinose (l ‐Ara4N) biosynthesis to result in cationic amine moiety addition to lipid A in many Enterobacteriaceae such as E. coli and Salmonella. In contrast, PmrAB is dispensable for CAMP resistance in E. cloacae. Interestingly, some ECC clusters exhibit colistin heteroresistance, where a subpopulation of cells exhibit clinically significant resistance levels compared to the majority population. We demonstrate that E. cloacae lipid A is modified with l ‐Ara4N to induce CAMP heteroresistance and the regulatory mechanism is independent of the PmrABEcl TCS. Instead, PhoPEcl binds to the arnBEcl promoter to induce l ‐Ara4N biosynthesis and PmrAB‐independent addition to the lipid A disaccharolipid. Therefore, PhoPQEcl contributes to regulation of CAMP heteroresistance in some ECC clusters. 相似文献
998.
Bulle Cécile Margni Manuele Patouillard Laure Boulay Anne-Marie Bourgault Guillaume De Bruille Vincent Cao Viêt Hauschild Michael Henderson Andrew Humbert Sebastien Kashef-Haghighi Sormeh Kounina Anna Laurent Alexis Levasseur Annie Liard Gladys Rosenbaum Ralph K. Roy Pierre-Olivier Shaked Shanna Fantke Peter Jolliet Olivier 《The International Journal of Life Cycle Assessment》2019,24(9):1653-1674
The International Journal of Life Cycle Assessment - This paper addresses the need for a globally regionalized method for life cycle impact assessment (LCIA), integrating multiple state-of-the-art... 相似文献
999.
Leão Susana Roux Philippe Loiseau Eléonore Junqua Guillaume Rosenbaum Ralph K. 《The International Journal of Life Cycle Assessment》2019,24(12):2255-2267
The International Journal of Life Cycle Assessment - A worldwide-regionalized water supply mix (WSmix) has been developed for use in life cycle assessment (LCA) studies. The WSmix is the... 相似文献
1000.
John H. Chau Cline Born Melodie A. McGeoch Dana Bergstrom Justine Shaw Aleks Terauds Mario Mairal Johannes J. Le Roux Bettine Jansen van Vuuren 《Molecular ecology》2019,28(14):3291-3305
The distribution of genetic variation in species is governed by factors that act differently across spatial scales. To tease apart the contribution of different processes, especially at intermediate spatial scales, it is useful to study simple ecosystems such as those on sub‐Antarctic oceanic islands. In this study, we characterize spatial genetic patterns of two keystone plant species, Azorella selago on sub‐Antarctic Marion Island and Azorella macquariensis on sub‐Antarctic Macquarie Island. Although both islands experience a similar climate and have a similar vegetation structure, they differ significantly in topography and geological history. We genotyped six microsatellites for 1,149 individuals from 123 sites across Marion Island and 372 individuals from 42 sites across Macquarie Island. We tested for spatial patterns in genetic diversity, including correlation with elevation and vegetation type, and clines in different directional bearings. We also examined genetic differentiation within islands, isolation‐by‐distance with and without accounting for direction, and signals of demographic change. Marion Island was found to have a distinct northwest–southeast divide, with lower genetic diversity and more sites with a signal of population expansion in the northwest. We attribute this to asymmetric seed dispersal by the dominant northwesterly winds, and to population persistence in a southwestern refugium during the Last Glacial Maximum. No apparent spatial pattern, but greater genetic diversity and differentiation between sites, was found on Macquarie Island, which may be due to the narrow length of the island in the direction of the dominant winds and longer population persistence permitted by the lack of extensive glaciation on the island. Together, our results clearly illustrate the implications of island shape and geography, and the importance of direction‐dependent drivers, in shaping spatial genetic structure. 相似文献