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排序方式: 共有130条查询结果,搜索用时 125 毫秒
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Thibault Teissier Valentine Quersin Viviane Gnemmi Mait Daroux Mike Howsam Florian Delguste Ccile Lemoine Chantal Fradin Ann‐Marie Schmidt Christelle Cauffiez Thierry Brousseau Franois Glowacki Frdric J. Tessier Eric Boulanger Marie Frimat 《Aging cell》2019,18(2)
Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE?/? C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/gfood) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE?/? mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE?/? mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE?/? mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE?/? mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE?/? mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging. 相似文献
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Sven Loebrich Elisa Clark Kristina Ladd Stefani Takahashi Anna Brousseau Seth Kitchener 《MABS-AUSTIN》2019,11(2):335-349
The extent and pattern of glycosylation on therapeutic antibodies can influence their circulatory half-life, engagement of effector functions, and immunogenicity, with direct consequences to efficacy and patient safety. Hence, controlling glycosylation patterns is central to any drug development program, yet poses a formidable challenge to the bio-manufacturing industry. Process changes, which can affect glycosylation patterns, range from manufacturing at different scales or sites, to switching production process mode, all the way to using alternative host cell lines. In the emerging space of biosimilars development, often times all of these aspects apply. Gaining a deep understanding of the direction and extent to which glycosylation quality attributes can be modulated is key for efficient fine-tuning of glycan profiles in a stage appropriate manner, but establishment of such platform knowledge is time consuming and resource intensive. Here we report an inexpensive and highly adaptable screening system for comprehensive modulation of glycans on antibodies expressed in CHO cells. We characterize 10 media additives in univariable studies and in combination, using a design of experiments approach to map the design space for tuning glycosylation profile attributes. We introduce a robust workflow that does not require automation, yet enables rapid process optimization. We demonstrate scalability across deep wells, shake flasks, AMBR-15 cell culture system, and 2 L single-use bioreactors. Further, we show that it is broadly applicable to different molecules and host cell lineages. This universal approach permits fine-tuned modulation of glycan product quality, reduces development costs, and enables agile implementation of process changes throughout the product lifecycle. 相似文献
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A Virulence and Antimicrobial Resistance DNA Microarray Detects a High Frequency of Virulence Genes in Escherichia coli Isolates from Great Lakes Recreational Waters 下载免费PDF全文
Katia Hamelin Guillaume Bruant Abdel El-Shaarawi Stephen Hill Thomas A. Edge Sadjia Bekal John Morris Fairbrother Jose Harel Christine Maynard Luke Masson Roland Brousseau 《Applied microbiology》2006,72(6):4200-4206
Escherichia coli is generally described as a commensal species with occasional pathogenic strains. Due to technological limitations, there is currently little information concerning the prevalence of pathogenic E. coli strains in the environment. For the first time, using a DNA microarray capable of detecting all currently described virulence genes and commonly found antimicrobial resistance genes, a survey of environmental E. coli isolates from recreational waters was carried out. A high proportion (29%) of 308 isolates from a beach site in the Great Lakes carried a pathotype set of virulence-related genes, and 14% carried antimicrobial resistance genes, findings consistent with a potential risk for public health. The results also showed that another 8% of the isolates had unusual virulence gene combinations that would be missed by conventional screening. This new application of a DNA microarray to environmental waters will likely have an important impact on public health, epidemiology, and microbial ecology in the future. 相似文献
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D. Audigeos L. Brousseau S. Traissac C. Scotti‐Saintagne I. Scotti 《Journal of evolutionary biology》2013,26(3):529-544
Unveiling the genetic basis of local adaptation to environmental variation is a major goal in molecular ecology. In rugged landscapes characterized by environmental mosaics, living populations and communities can experience steep ecological gradients over very short geographical distances. In lowland tropical forests, interspecific divergence in edaphic specialization (for seasonally flooded bottomlands and seasonally dry terra firme soils) has been proven by ecological studies on adaptive traits. Some species are nevertheless capable of covering the entire span of the gradient; intraspecific variation for adaptation to contrasting conditions may explain the distribution of such ecological generalists. We investigated whether local divergence happens at small spatial scales in two stands of Eperua falcata (Fabaceae), a widespread tree species of the Guiana Shield. We investigated Single Nucleotide Polymorphisms (SNP) and sequence divergence as well as spatial genetic structure (SGS) at four genes putatively involved in stress response and three genes with unknown function. Significant genetic differentiation was observed among sub‐populations within stands, and eight SNP loci showed patterns compatible with disruptive selection. SGS analysis showed genetic turnover along the gradients at three loci, and at least one haplotype was found to be in repulsion with one habitat. Taken together, these results suggest genetic differentiation at small spatial scale in spite of gene flow. We hypothesize that heterogeneous environments may cause molecular divergence, possibly associated to local adaptation in E. falcata. 相似文献
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D G Silverman D A Brousseau K J Norton N Clark H Weinberg 《Plastic and reconstructive surgery》1989,84(5):794-799
The present study evaluated the ability of DHV-PGE2ME, a topically effective 16-vinyl prostaglandin E2 analogue, to improve the tolerance of skin flaps to a period of ischemia. DHV-PGE2ME and placebo were applied to bilateral island flaps on 70 anesthetized rats; then the vascular pedicle of each flap was clamped for 10 hours. Treated flaps evidenced significantly better reperfusion, as documented by quantification of fluorescein dye delivery at 90 minutes after clamp release, and they had significantly greater ultimate viability (p less than 0.05, by ANOVA). While less than 3 percent of untreated flaps survived, those treated with 1.75 and 17.5 microgram/cm2 of drug evidenced 76 and 86 percent survival, respectively. Treatment of a given flap did not affect its contralateral mate, since there was no evidence of a systemic effect. Especially since its effect can be limited to the site of application, DHV-PGE2ME should be valuable for the treatment of compromised perfusion in a variety of settings. 相似文献
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Thanks to the techniques of recombinant DNA, there is now abundant sequence information on several endotoxin genes of Bacillus thuringiensis. The task of correlating this sequence information with the economically important aspects of the toxins such as insect specificity, LD(50) and speed of kill is now under worldwide investigation. Progress has also been made on understanding the mechanism of action of the toxins and on identifying the parts of the protoxin which are important in toxicity. Taken together, the mechanistic data and the sequence information allow the first attempts at rational design of mutant endotoxin genes and greatly facilitate the transfer of those genes to other organisms such as plants. More information is still needed, however, as to the nature of the binding site of the toxin and on the three-dimensional structure of the activated toxins. 相似文献
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Margaret E. Brousseau John S. Millar Margaret R. Diffenderfer Chorthip Nartsupha Bela F. Asztalos Megan L. Wolfe James P. Mancuso Andres G. Digenio Daniel J. Rader Ernst J. Schaefer 《Journal of lipid research》2009,50(7):1456-1462
This study was designed to establish the mechanism responsible for the increased apolipoprotein (apo) A-II levels caused by the cholesteryl ester transfer protein inhibitor torcetrapib. Nineteen subjects with low HDL cholesterol (<40 mg/dl), nine of whom were also treated with 20 mg of atorvastatin daily, received placebo for 4 weeks, followed by 120 mg of torcetrapib daily for the next 4 weeks. Six subjects in the nonatorvastatin cohort participated in a third phase, in which they received 120 mg of torcetrapib twice daily for 4 weeks. At the end of each phase, subjects underwent a primed-constant infusion of [5,5,5-2H3]l-leucine to determine the kinetics of HDL apoA-II. Relative to placebo, torcetrapib significantly increased apoA-II concentrations by reducing HDL apoA-II catabolism in the atorvastatin (−9.4%, P < 0.003) and nonatorvastatin once- (−9.9%, P = 0.02) and twice- (−13.2%, P = 0.02) daily cohorts. Torcetrapib significantly increased the amount of apoA-II in the α-2-migrating subpopulation of HDL when given as monotherapy (27%, P < 0.02; 57%, P < 0.003) or on a background of atorvastatin (28%, P < 0.01). In contrast, torcetrapib reduced concentrations of apoA-II in α-3-migrating HDL, with mean reductions of −14% (P = 0.23), −18% (P < 0.02), and −18% (P < 0.01) noted during the atorvastatin and nonatorvastatin 120 mg once- and twice-daily phases, respectively. Our findings indicate that CETP inhibition increases plasma concentrations of apoA-II by delaying HDL apoA-II catabolism and significantly alters the remodeling of apoA-II-containing HDL subpopulations. 相似文献