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81.
Laëtitia Coudray Renata Marcia de Figueiredo Stéphanie Duez Sylvie Cortial 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):972-985
With the aim of creating new bisubstrate inhibitors of protein farnesyltransferase (FTase), new carboxylic farnesyl pyrophosphate analogues have been designed and synthesized. The original structures are built around three elements: a prenyl moiety, a 1,4-diacid motif and an imidazole ring. All the compounds were evaluated for their ability to inhibit FTase and compared with the corresponding derivatives lacking the imidazole ring, synthesized for that purpose. These new compounds are not bisubstrate inhibitors probably because the imidazole ring is not in the right position to interact with the zinc atom. However these derivatives display FPP competitive inhibition with a good activity in the carboxylic farnesyl pyrophosphate analogues series. 相似文献
82.
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
83.
Sylvie Pochet Laurence Dugué Monica Sala Valérie Pézo Simon Wain-Hobson 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1749-1752
Abstract The use of 5′-triphosphate of 1-(2-deoxy-β-D-ribofuranosyl)imidazole-4-carboxamide (dYTP) in DNA amplification reaction in place of dATP or dGTP yielded mutations frequencies of 3–4×10?2 per base per amplification. A reasonable proportion of transversions (11–15%) was observed in the absence of deletions and insertions. 相似文献
84.
85.
Benjamin Proshek Lindsay A. Crawford Corey S. Davis Sylvie Desjardins Allison E. Henderson Felix A. H. Sperling 《Journal of Insect Conservation》2013,17(1):155-170
Like many species, the Mormon Metalmark butterfly (Apodemia mormo) has been given conservation ranking in Canada based on limited data. This species is widespread across western North America, but has only two populations in Canada: an “endangered” population in the Similkameen valley of British Columbia, and a “threatened” population in Grasslands National Park (GNP) in Saskatchewan. Here we present genetic data from 1498 base pairs of the cytochrome oxidase I gene sequence and six novel microsatellite loci in order to assess (1) whether the two populations are related, (2) the degree to which they are genetically diverse and demographically stable, and (3) what their relationships are to the nearest unranked populations of A. mormo across the Canada-United States border. Our principal conclusion is that the two populations are not closely related genetically. We also found that the British Columbia population is genetically depauperate and, with the exception of the nearest neighboring populations across the border, not recently genetically connected to other populations in the Pacific Northwest. In comparison, the Saskatchewan population is genetically diverse, and gene flow occurs with several other eastern populations. Population structure was not detected within either the British Columbia or the Saskatchewan populations. This research supports the prior conservation rankings of both populations and provides new insight that will help to inform future management decisions for the Canadian populations of this charismatic butterfly. 相似文献
86.
87.
Ghulam Hussain Florent Schmitt Alexandre Henriques Thiebault Lequeu Frederique Rene Fran?oise Bindler Sylvie Dirrig-Grosch Hugues Oudart Lavinia Palamiuc Marie-Helene Metz-Boutigue Luc Dupuis Eric Marchioni Jose-Luis Gonzalez De Aguilar Jean-Philippe Loeffler 《PloS one》2013,8(6)
The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles. 相似文献
88.
David Leaper Christian Münter Sylvie Meaume Alessandro Scalise Nacho Blanes Mompó Birte Petersen Jakobsen Finn Gottrup 《PloS one》2013,8(7)
Background
Venous leg ulcers are common, troublesome, and their failure to heal is often related to a heavy bio-burden. Ionized silver has both anti-inflammatory and antimicrobial properties. The ulcer healing properties of the silver releasing foam dressing Biatain Ag has been examined in 4 randomized controlled trials (RCTs).Aim
To evaluate ulcer healing through a meta-analytic approach after treatment with either Biatain Ag or a non-active dressing.Patients and Methods
685 subjects with pure or mixed hard-to-heal venous leg ulcers were included in the meta-analysis.Results
Biatain Ag showed a significant treatment effect (p<0.0001), responder rate (p<0.001), and healing rate (p = 0.002).Conclusion
The meta-analysis of the 4 RCTs provided statistical significant evidence to support the use of Biatain Ag dressing in treatment of hard-to-heal venous leg ulcers. 相似文献89.
Migraine is sexually dimorphic and associated in 20–30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17β-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments. 相似文献
90.
Claire Amiable Sylvie Pochet André Padilla Gilles Labesse Pierre Alexandre Kaminski 《PloS one》2013,8(11)
The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2’-deoxyribonucleoside 5’-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N
6-substituted AMPs, and among them, cytotoxic cytokinin riboside 5’-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth. 相似文献