Root Development in Medicago truncatula: Lessons from Genetics to Functional Genomics

International audienc

The evolution of living beings started with prokaryotes and in interaction with prokaryotes

In natural world, no organism exists in absolute isolation, and thus every organism must interact with the environment and other organisms. Next-generation sequencing technologies are increasingly revealing that most of the cells in the environment resist cultivation in the laboratory and several prokaryotic divisions have no known cultivated representatives. Based on this, we hypothesize that species that live together in the same ecosystem are more or less dependent upon each other and are very large in diversity and number, outnumbering those that can be isolated in single-strain laboratory culture. In natural environments, bacteria and archaea interact with other organisms (viruses, protists, fungi, animals, plants, and human) in complex ecological networks, resulting in positive, negative, or no effect on one or another of the interacting partners. These interactions are sources of ecological forces such as competitive exclusion, niche partitioning, ecological adaptation, or horizontal gene transfers, which shape the biological evolution. In this chapter, we review the biological interactions involving prokaryotes in natural ecosystems, including plant, animal, and human microbiota, and give an overview of the insights into the evolution of living beings. We conclude that studies of biological interactions, including multipartite interactions, are sources of novel knowledge related to the biodiversity of living things, the functioning of ecosystems, the evolution of the cellular world, and the ecosystem services to the living beings

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients