Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Transfer of resistance against soil-borne wheat mosaic virus from Triticum monococcum to hexaploid wheat (T. aestivum)

Resistance to soil-borne viruses as Soil-borne Wheat Mosaic Virus (SBWMV) has gained evident importance in wheat research and breeding. Very few varieties of bread and durum wheat are resistant to these viruses. Search for new sources of SBWMV is conducted worldwide and loci causing resistance have been described on the B and D genomes of tetraploid and hexaploid wheat. In the present study, a gene locus was identified on the A genome of Triticum monococcum and was successfully transferred to hexaploid wheat. In hexaploid wheat, it is expressed in a stable dominant manner. As this is the first SBWMV resistance gene located on the A genome, this locus is proposed as Sbm3

Adjustment of diurnal starch turnover to short days: depletion of sugar during the night leads to a temporary inhibition of carbohydrate utilization, accumulation of sugars and post-translational activation of ADP-glucose pyrophosphorylase in the following light period

A larger proportion of the fixed carbon is retained as starch in the leaf in short days, providing a larger store to support metabolism and carbon export during the long night. The mechanisms that facilitate this adjustment of the sink-source balance are unknown. Starchless pgm mutants were analysed to discover responses that are triggered when diurnal starch turnover is disturbed. Sugars accumulated to high levels during the day, and fell to very low levels by the middle of the night. Sugars rose rapidly in the roots and rosette after illumination, and decreased later in the light period. Global transcript profiling revealed only small differences between pgm and Col0 at the end of the day but large differences at the end of the night, when pgm resembled Col0 after a 4-6 h prolongation of the night and many genes required for biosynthesis and growth were repressed [Plant J. 37 (2004) 914]. It is concluded that transient sugar depletion at the end of the night inhibits carbon utilization at the start of the ensuing light period. A second set of experiments investigated the stimulation of starch synthesis in response to short days in wild-type Col0. In short days, sugars were very low in the roots and rosette at the end of the dark period, and after illumination accumulated rapidly in both organs to levels that were higher than in long days. The response resembles pgm, except that carbohydrate accumulated in the leaf as starch instead of sugars. A similar response was found after transfer from long to short days. Inclusion of sugar in the rooting medium attenuated the stimulation of starch synthesis. Post-translational activation of ADP-glucose pyrophosphorylase (AGPase) was increased in pgm, and in Col0 in short days. It is concluded that starch synthesis is stimulated in short day conditions because sugar depletion at the end of the night triggers a temporary inhibition of growth and carbohydrate utilization in the first part of the light period, leading to transient accumulation of sugar and activation of AGPase

Development and validation of L allele-specific markers in Capsicum

Tobamovirus is one of most destructive viruses in Capsicum. Accordingly, the L locus, a resistance gene against tobamoviruses, has been used for pepper breeding programs. Previously, the L 3 gene, one of the L alleles, was isolated through map-based cloning, and a L 4 gene candidate was isolated by homology-based PCR methods. Here, the L4segF&R marker was developed based on the leucine-rich repeat (LRR) region of the L 4 candidate, and co-segregation analysis was performed using two L 4 -segregating F2 populations derived from the commercial cultivars Special and Myoung-sung. The L4segF&R marker was located within 0.3 cM of the L 4 gene but did not completely co-segregate with the L 4 gene, indicating that the candidate is not actually L 4 . To confirm the mapping result, L4segF&R genotypes of L 4 -containing breeding lines from three different seed companies were analyzed, resulting in the identification of several recombinants in the breeding lines.Based on these results, we postulate several genetic models that show different introgression histories and genetic structures for the L 4 -containing segment in different breeding lines. All of the models demonstrate that resistance conferred by the L 4 segment could not be explained by the L 4 gene candidate alone. Although the presence of the L 4 gene candidate could not fully explain the L 4 resistance, we were able to develop allele-specific markers for the L locus using the candidate sequence. To develop allele-specific markers for the L locus, HRM analysis was performed using primer pairs based on the LRR sequence of the L 4 gene candidate. When commercial breeding lines homozygous for L 0 , L 1 , L 2 , L 3 or L 4 were analyzed, L4RP-3F/L4RP-3R correctly detected the L allele in 90 out of 91 lines. We believe that the L allele-specific marker developed in the study provides a solution for pepper breeders developing improved resistance lines against tobamoviruses