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101.
Frédégonde About Tiphaine Oudot-Mellakh Jonathan Niay Pascaline Rabiéga Vincent Pedergnana Darragh Duffy Philippe Sultanik Carole Cagnot Fabrice Carrat Patrick Marcellin Fabien Zoulim Dominique Larrey Christophe Hézode Hélène Fontaine Jean-Pierre Bronowicki Stanislas Pol Matthew L. Albert Ioannis Theodorou Aurélie Cobat Laurent Abel ANRS CO-CUPIC study group 《PloS one》2015,10(12)
Background
Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.Patients and Methods
A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model.Results
None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50–3.70], P = 2x10-4). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10-5).Conclusion
Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy. 相似文献102.
Izabela A. Rodenhuis-Zybert Júlia M. da Silva Voorham Silvia Torres Denise van de Pol Jolanda M. Smit 《PLoS neglected tropical diseases》2015,9(3)
Humoral immunity plays an important role in controlling dengue virus (DENV) infection. Antibodies (Abs) developed during primary infection protect against subsequent infection with the same dengue serotype, but can enhance disease following secondary infection with a heterologous serotype. A DENV virion has two surface proteins, envelope protein E and (pre)-membrane protein (pr)M, and inefficient cleavage of the prM protein during maturation of progeny virions leads to the secretion of immature and partially immature particles. Interestingly, we and others found that historically regarded non-infectious prM-containing DENV particles can become highly infectious in the presence of E- and prM-Abs. Accordingly, we hypothesized that these virions contribute to the exacerbation of disease during secondary infection. Here, we tested this hypothesis and investigated the ability of acute sera of 30 DENV2-infected patients with different grades of disease severity, to bind, neutralize and/or enhance immature DENV2. We found that a significant fraction of serum Abs bind to the prM protein and to immature virions, but we observed no significant difference between the disease severity groups. Furthermore, functional analysis of the Abs did not underscore any specific correlation between the neutralizing/enhancing activity towards immature DENV2 and the development of more severe disease. Based on our analysis of acute sera, we conclude that Abs binding to immature virions are not a discriminating factor in dengue pathogenesis. 相似文献
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105.
Glucuronoyl esterase is a novel carbohydrate esterase recently discovered in the cellulolytic system of the wood-rotting fungus
Schizophyllum commune on the basis of its ability to hydrolyze methyl ester of 4-O-methyl-d-glucuronic acid. This substrate was not fully corresponding to the anticipated function of the enzyme to hydrolyze esters
between xylan-bound 4-O-methyl-d-glucuronic acid and lignin alcohols occurring in plant cell walls. In this work we showed that the enzyme was capable of
hydrolyzing two synthetic compounds that mimic the ester linkages described in lignin-carbohydrate complexes, esters of 4-O-methyl-d-glucuronic and d-glucuronic acid with 3-(4-methoxyphenyl)propyl alcohol. A comparison of kinetics of hydrolysis of methyl and 3-(4-methoxyphenyl)propyl
esters indicated that the glucuronoyl esterase recognizes the uronic acid part of the substrates better than the alcohol type.
The catalytic efficiency of the enzyme was much higher with the ester of 4-O-methyl-d-glucuronic acid than with that of d-glucuronic acid. Examination of the action of glucuronoyl esterase on a series of methyl esters of 4-O-methyl-d-glucopyranuronosyl residues α-1,2-linked to xylose and several xylooligosaccharides suggested that the rate of deesterification
is independent of the character of the carbohydrate part glycosylated by the 4-O-methyl-d-glucuronic acid. 相似文献
106.
In most species, some individuals delay reproduction or occupy inferior breeding positions. The queue hypothesis tries to explain both patterns by proposing that individuals strategically delay breeding (queue) to acquire better breeding or social positions. In 1995, Ens, Weissing, and Drent addressed evolutionarily stable queuing strategies in situations with habitat heterogeneity. However, their model did not consider the non-mutually exclusive individual quality hypothesis, which suggests that some individuals delay breeding or occupy inferior breeding positions because they are poor competitors. Here we extend their model with individual differences in competitive abilities, which are probably plentiful in nature. We show that including even the smallest competitive asymmetries will result in individuals using queuing strategies completely different from those in models that assume equal competitors. Subsequently, we investigate how well our models can explain settlement patterns in the wild, using a long-term study on oystercatchers. This long-lived shorebird exhibits strong variation in age of first reproduction and territory quality. We show that only models that include competitive asymmetries can explain why oystercatchers' settlement patterns depend on natal origin. We conclude that predictions from queuing models are very sensitive to assumptions about competitive asymmetries, while detecting such differences in the wild is often problematic. 相似文献
107.
Ray AD Magalang UJ Michlin CP Ogasa T Krasney JA Gosselin LE Farkas GA 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,293(1):R372-R378
Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O(2) levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats (P < 0.05). The pharyngeal pressure associated with airway collapse (P(crit)) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline P(crit) was more positive (more collapsible) in lean but not obese rats following 12 wk of IH (P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased P(crit)) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms. 相似文献
108.
An infinite number of 2D patterns on the retina can correspond to a single 3D object. How do visual systems resolve this ill-posed problem and recognize objects from only a few 2D retinal projections in varied exposure conditions? Theories of object recognition rely on the nonaccidental statistics of edge properties, mainly symmetry, collinearity, curvilinearity, and cotermination. These statistics are determined by the image-formation process (i.e., the 2D retinal projection of a 3D object ); their existence under a range of viewpoints enables viewpoint-invariant recognition. An important question in behavioral biology is whether the visual systems of nonmammalian animals have also evolved biases to utilize nonaccidental statistics . Here, we trained humans and pigeons to recognize four shapes. With the Bubbles technique, we determined which stimulus properties both species used to recognize the shapes. Both humans and pigeons used cotermination, the most diagnostic nonaccidental property of real-world objects, despite evidence from a model computer observer that cotermination was not the most diagnostic pictorial information in this particular task. This result reveals that a nonmammalian visual system that is different anatomically from the human visual system is also biased to recognize objects from nonaccidental statistics. 相似文献
109.
On divide-and-conquer strategies for parsimony analysis of large data sets: Rec-I-DCM3 versus TNT 总被引:1,自引:0,他引:1
Roshan et al. recently described a "divide-and-conquer" technique for parsimony analysis of large data sets, Rec-I-DCM3, and stated that it compares very favorably to results using the program TNT. Their technique is based on selecting subsets of taxa to create reduced data sets or subproblems, finding most-parsimonious trees for each reduced data set, recombining all parts together, and then performing global TBR swapping on the combined tree. Here, we contrast this approach to sectorial searches, a divide-and-conquer algorithm implemented in TNT. This algorithm also uses a guide tree to create subproblems, with the first-pass state sets of the nodes that join the selected sectors with the rest of the topology; this allows exact length calculations for the entire topology (that is, any solution N steps shorter than the original, for the reduced subproblem, must also be N steps shorter for the entire topology). We show here that, for sectors of similar size analyzed with the same search algorithms, subdividing data sets with sectorial searches produces better results than subdividing with Rec-I-DCM3. Roshan et al.'s claim that Rec-I-DCM3 outperforms the techniques in TNT was caused by a poor experimental design and algorithmic settings used for the runs in TNT. In particular, for finding trees at or very close to the minimum known length of the analyzed data sets, TNT clearly outperforms Rec-I-DCM3. Finally, we show that the performance of Rec-I-DCM3 is bound by the efficiency of TBR implementation for the complete data set, as this method behaves (after some number of iterations) as a technique for cyclic perturbations and improvements more than as a divide-and-conquer strategy. 相似文献
110.
Baart GJ Zomer B de Haan A van der Pol LA Beuvery EC Tramper J Martens DE 《Genome biology》2007,8(7):R136