The Arabidopsis RPM1 gene confers resistance against Pseudomonas syringae expressing either the AvrRpm1 or the AvrB type III effector protein. We present an exhaustive genetic screen for mutants that ...no longer recognize avrRpm1. Using an inducible avrRpm1 expression system, we identified 110 independent mutations. These mutations represent six complementation groups. None discriminates between avrRpm1 and avrB recognition. We identified 95 rpm1 alleles and present a detailed structure-function analysis of the RPM1 protein. Several rpm1 mutants retain partial function, and we deduce that their residual activity is dependent on the level of avrRpm1 signal. In these mutants, the hypersensitive response remains activated if the signal goes above a certain threshold. Missense mutations in rpm1 are highly enriched in the nucleotide binding domain, suggesting that this region plays a key role either in the hypersensitive response associated with RPM1 activation or in RPM1 stability. Cluster analysis of rpm1 alleles defines functionally important residues that are highly conserved between nucleotide binding site leucine-rich repeat R proteins and those that are unique to RPM1. Regions of RPM1 to which no loss-of-function alleles map may represent domains in which variation is tolerated and may contribute to the evolution of new R gene specificities.
We report on photometric observations of two WZ Sge-type dwarf novae, MASTER OT J211258.65+242145.4 and MASTER OT J203749.39+552210.3, which underwent outbursts in 2012. Early superhumps were ...recorded in both systems. During the superoutburst plateau, ordinary superhumps with a period of 0.060291(4) d (MASTER J211258) and with 0.061368(11) d (MASTER J203749) on average were observed. MASTERJ211258 and MASTERJ203749 exhibited eight post-superoutburst rebrightenings and more than four, respectively. In the final part of the superoutburst, an increase in superhump period was seen in both systems. We made a survey of WZSge-type dwarf novae with multiple rebrightenings, and confirmed that the superhump periods of WZSge-type dwarf novae with multiple rebrightenings were longer than those of WZSge-type dwarf novae without a rebrightening. Although WZSge-type dwarf novae with multiple rebrightenings have been thought to be likely candidates for period bouncers based on their low mass ratio (q), inferred from the period of fully grown (stage B) superhumps, our new method of using the period of growing superhumps (stage A superhumps), however, implies higher q's than those expected from stage B superhumps. These q values appear to be consistent with the duration of the stage A superoutbursts, which likely reflects the growth time of the 3W1 resonance. We present a working hypothesis that the small fractional superhump excesses for stage B superhumps in these systems may be explained by a gas pressure effect that works more efficiently in these systems than in ordinary SU UMa-type dwarf novae. This result forms a new picture that WZSge-type dwarf novae with multiple rebrightenings and SU UMa-type ones without a rebrightening (they are not period bouncers) are located in the same place on the evolutionary track.
Abstract
We report on photometric observations of two dwarf novae, OT J075418.7+381225 and OT J230425.8+062546, which showed superoutbursts in 2013 (OT J075418) and in 2011 (OT J230425). Their mean ...periods of the superhump were 0.0722403(26) d (OT J075418) and 0.067317(35) d (OT J230425). These objects showed a very long growth stage of the superhump (stage A) and a large period decrease in the stage A–B transition. The long stage A suggests slow evolution of the superhump due to the very small mass ratio of these objects. The declining rates during the plateau phase in the superoutburst of these objects were lower than those of SU UMa-type dwarf novae (DNe) with a similar superhump period. These properties were similar to those of SSS J122221.7−311523, the most likely candidate for the period bouncer. Therefore, these two DNe are regarded as likely candidates for the period bouncer. We estimated the number density of period bouncers roughly from our observations for the last five years. There is a possibility that these WZ Sge-type DNe with unusual outburst properties might account for the missing population of the period bouncer suggested by the evolutionary scenario.
Complex retroviruses, retroelements and their hosts Montpellier, France 21-23 September 2009 Author details 1-Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, ...Columbia University, College of Physicians and Surgeons, New York, NY, USAEMPTY 2-Center for Infections and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, PR ChinaEMPTY 3-Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY, USAEMPTY Supplemental Information: ... we found that similar silencing occurs at the distinct PBS for at least one other tRNA (namely, Lys1,2) utilized by such viruses as visna and spuma.
There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy ...targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.
A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval CI, 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001).
In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)
We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes ...mellitus who were at high risk for cardiovascular disease.
We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.
The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval CI, 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction).
The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)
Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year ...outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events.
We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial.
Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval CI, 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups.
As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.).
We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type ...2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.
In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy.
At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval CI, 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29).
Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)
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