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71.
Hugo Cayuela Quentin Rougemont Martin Laporte Claire Mrot Eric Normandeau Yann Dorant Ole K. Trresen Siv Nam Khang Hoff Sissel Jentoft Pascal Sirois Martin Castonguay Teunis Jansen Kim Praebel Marie Clment Louis Bernatchez 《Molecular ecology》2020,29(13):2379-2398
Gene flow has tremendous importance for local adaptation, by influencing the fate of de novo mutations, maintaining standing genetic variation and driving adaptive introgression. Furthermore, structural variation as chromosomal rearrangements may facilitate adaptation despite high gene flow. However, our understanding of the evolutionary mechanisms impending or favouring local adaptation in the presence of gene flow is still limited to a restricted number of study systems. In this study, we examined how demographic history, shared ancestral polymorphism, and gene flow among glacial lineages contribute to local adaptation to sea conditions in a marine fish, the capelin (Mallotus villosus). We first assembled a 490‐Mbp draft genome of M. villosus to map our RAD sequence reads. Then, we used a large data set of genome‐wide single nucleotide polymorphisms (25,904 filtered SNPs) genotyped in 1,310 individuals collected from 31 spawning sites in the northwest Atlantic. We reconstructed the history of divergence among three glacial lineages and showed that they probably diverged from 3.8 to 1.8 million years ago and experienced secondary contacts. Within each lineage, our analyses provided evidence for large Ne and high gene flow among spawning sites. Within the Northwest Atlantic lineage, we detected a polymorphic chromosomal rearrangement leading to the occurrence of three haplogroups. Genotype–environment associations revealed molecular signatures of local adaptation to environmental conditions prevailing at spawning sites. Our study also suggests that both shared polymorphisms among lineages, resulting from standing genetic variation or introgression, and chromosomal rearrangements may contribute to local adaptation in the presence of high gene flow. 相似文献
72.
Engelhardt Ilonka C. Niklaus Pascal A. Bizouard Florian Breuil Marie-Christine Rouard Nadine Deau Florence Philippot Laurent Barnard Romain L. 《Plant and Soil》2021,461(1-2):151-162
Plant and Soil - Contrasting nutrient-acquisition strategies would explain why species differ in their distribution in relation to soil phosphorus (P) availability, promoting diversity. However,... 相似文献
73.
Irmina Diala Nicole Wagner Frédérique Magdinier Marina Shkreli Serge Bauwens Caroline Schluth‐Bolard Thomas Simonet Valérie M Renault Jing Ye Abdelnnadir Djerbi Pascal Pineau Jinkuk Choi Steven Artandi Anne Dejean Eric Gilson 《EMBO reports》2013,14(4):356-363
The DNA‐binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/β‐catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β‐catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β‐catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β‐catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis. 相似文献
74.
Marie-Pierre Lézé Pascal Marchand Denis Loquet Manuela Kogler Guillaume Le Baut 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):549-557
The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a–h and 28a–h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC50 and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28?g) was a highly potent and selective aromatase inhibitor with IC50 value of 0.025?μM. 28?g was also a weak inhibitor of androstenedione synthesis. 相似文献
75.
Fabrice Pagniez Hiam Abdala-Valencia Pascal Marchand Marc Le Borgne Guillaume Le Baut Sylvie Robert-Piessard 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):277-283
Two 3-(α-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 ± 0.1 and 6.4 ± 0.1 μM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 μM and PM19 had an IC50 of 1.3 μM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse. 相似文献
76.
Aurélie Hurtevent Morgan Le Naour Veronique Leclerc Pascal Carato Patricia Melnyk Nathalie Hennuyer 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):524-538
Abstract A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44?b displaying the best in vitro pharmacological profile. Compound 44?b acted as a very potent full PPARγ agonist and a weak partial agonist on the PPARα receptor subtype. Compound 44?b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPARγ modulator (SPPARγM). 相似文献
77.
Sébastien Ottaviani Anna Moltó Hang-Korng Ea Séverine Neveu Ghislaine Gill Lauren Brunier Elisabeth Palazzo Olivier Meyer Pascal Richette Thomas Bardin Yannick Allanore Frédéric Lioté Maxime Dougados Philippe Dieudé 《Arthritis research & therapy》2013,15(5):R123
Introduction
Gout is a common arthritis that occurs particularly in patients who frequently have associated comorbidities that limit the use of conventional therapies. The main mechanism of crystal-induced inflammation is interleukin-1 production by activation of the inflammasome. We aimed to evaluate the efficacy and tolerance of anakinra in gouty patients.Methods
We conducted a multicenter retrospective review of patients receiving anakinra for gouty arthritis. We reviewed the response to treatment, adverse events and relapses.Results
We examined data for 40 gouty patients (32 men; mean age 60.0 ± 13.9 years) receiving anakinra. Mean disease duration was 8.7 ± 8.7 years. All patients showed contraindications to and/or failure of at least two conventional therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0 (20.0 to 32.5) mm, P <0.0001), as was median C-reactive protein (CRP) level (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P <0.0001). After a median follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with long-term use of anakinra, were noted.Conclusions
Anakinra may be efficient in gouty arthritis, is relatively well tolerated with short-term use, and could be a relevant option in managing gouty arthritis when conventional therapies are ineffective or contraindicated. Its long-term use could be limited by infectious complications. 相似文献78.
Indrajit Giri Pascal J. Bolon Chung K. Chu 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):183-204
Abstract A general method for the synthesis of 2′-C-α-methyl-2′,3′-dideoxynucleosides is presented. Stereofacial selectivity of the 2-C-methylation reaction of γ-lactone has been investigated, in which the presence of a bulky group at the 5-hydroxymethyl produced the α-isomer as a major product. During glycosylation, the α-methyl group directed the formation of nucleosides in favor of the ß-isomer. This methodology is applied to the synthesis of some new pyrimidine and purine nucleosides. 相似文献
79.
DENS: data center energy-efficient network-aware scheduling 总被引:1,自引:0,他引:1
In modern data centers, energy consumption accounts for a considerably large slice of operational expenses. The existing work in data center energy optimization is focusing only on job distribution between computing servers based on workload or thermal profiles. This paper underlines the role of communication fabric in data center energy consumption and presents a scheduling approach that combines energy efficiency and network awareness, named DENS. The DENS methodology balances the energy consumption of a data center, individual job performance, and traffic demands. The proposed approach optimizes the tradeoff between job consolidation (to minimize the amount of computing servers) and distribution of traffic patterns (to avoid hotspots in the data center network). 相似文献
80.
Frédéric Pinel Bernabé Dorronsoro Johnatan E. Pecero Pascal Bouvry Samee U. Khan 《Cluster computing》2013,16(3):421-433
The sensitivity analysis of a Cellular Genetic Algorithm (CGA) with local search is used to design a new and faster heuristic for the problem of mapping independent tasks to a distributed system (such as a computer cluster or grid) in order to minimize makespan (the time when the last task finishes). The proposed heuristic improves the previously known Min-Min heuristic. Moreover, the heuristic finds mappings of similar quality to the original CGA but in a significantly reduced runtime (1,000 faster). The proposed heuristic is evaluated across twelve different classes of scheduling instances. In addition, a proof of the energy-efficiency of the algorithm is provided. This convergence study suggests how additional energy reduction can be achieved by inserting low power computing nodes to the distributed computer system. Simulation results show that this approach reduces both energy consumption and makespan. 相似文献