Association genetics is a powerful method to track gene polymorphisms responsible for phenotypic variation, since it takes advantage of existing collections and historical recombination to study the ...correlation between large genetic diversity and phenotypic variation. We used a collection of 375 maize (Zea mays ssp. mays) inbred lines representative of tropical, American, and European diversity, previously characterized for genome-wide neutral markers and population structure, to investigate the roles of two functionally related candidate genes, Opaque2 and CyPPDK1, on kernel quality traits. Opaque2 encodes a basic leucine zipper transcriptional activator specifically expressed during endosperm development that controls the transcription of many target genes, including CyPPDK1, which encodes a cytosolic pyruvate orthophosphate dikinase. Using statistical models that correct for population structure and individual kinship, Opaque2 polymorphism was found to be strongly associated with variation of the essential amino acid lysine. This effect could be due to the direct role of Opaque2 on either zein transcription, zeins being major storage proteins devoid of lysine, or lysine degradation through the activation of lysine ketoglutarate reductase. Moreover, we found that a polymorphism in the Opaque2 coding sequence and several polymorphisms in the CyPPDK1 promoter nonadditively interact to modify both lysine content and the protein-versus-starch balance, thus revealing the role in quantitative variation in plants of epistatic interactions between a transcriptional activator and one of its target genes.
A series of cubic mesoporous silica materials exhibiting large cage-like cavities (up to 12.5
nm) interconnected through windows (
Im3m symmetry group) and with a mesopore volume as high as 1.30
cm
3
...g
−1 have been synthesized for the first time by using a new polyalkylene oxide-based triblock copolymer (PEO
140PPO
39PEO
140). The ability of this new triblock copolymer surfactant to act as a template for well-defined multidirectional pore network cubic silica particles, exhibiting tailored porous characteristics, was shown to depend on the synthesis conditions, in particular the acidity and temperature, as well as the presence of a cationic co-surfactant. These parameters influence the aggregation of nanoparticles either in micron-sized particles with different nanoparticles coalescence degrees or in blocks of aggregated nanoparticles. The aforementioned materials were characterized by small angle X-ray powder diffraction, nitrogen adsorption, scanning and transmission electronic microscopy, while the hydrodynamic diameters of the new triblock copolymer species were determined in situ by dynamic light scattering.
Association genetics is a powerful method to track gene polymorphisms responsible for phenotypic variation, since it takes advantage of existing collections and historical recombination to study the ...correlation between large genetic diversity and phenotypic variation. We used a collection of 375 maize (Zea mays ssp. mays) inbred lines representative of tropical, American, and European diversity, previously characterized for genome-wide neutral markers and population structure, to investigate the roles of two functionally related candidate genes, Opaque2 and CyPPDK1, on kernel quality traits. Opaque2 encodes a basic leucine zipper transcriptional activator specifically expressed during endosperm development that controls the transcription of many target genes, including CyPPDK1, which encodes a cytosolic pyruvate orthophosphate dikinase. Using statistical models that correct for population structure and individual kinship, Opaque2 polymorphism was found to be strongly associated with variation of the essential amino acid lysine. This effect could be due to the direct role of Opaque2 on either zein transcription, zeins being major storage proteins devoid of lysine, or lysine degradation through the activation of lysine ketoglutarate reductase. Moreover, we found that a polymorphism in the Opaque2 coding sequence and several polymorphisms in the CyPPDK1 promoter nonadditively interact to modify both lysine content and the protein-versus-starch balance, thus revealing the role in quantitative variation in plants of epistatic interactions between a transcriptional activator and one of its target genes.
Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to ...evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer BCLC 0) in patients with an annual HCC risk >3%.
French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs.
Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective.
In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection.
The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes.
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•HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance.•Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified.•Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.
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