The intracellular ROS accumulation in elicitor‐induced immunity requires the multiple organelle‐targeted Arabidopsis NPK1‐related protein kinases

Recognition at the plasma membrane of danger signals (elicitors) belonging to the classes of the microbe/pathogen‐ and damage‐associated molecular patterns is a key event in pathogen sensing by plants and is associated with a rapid activation of immune responses. Different cellular compartments, including plasma membrane, chloroplasts, nuclei and mitochondria, are involved in the immune cellular program. However, how pathogen sensing is transmitted throughout the cell remains largely to be uncovered. Arabidopsis NPK1‐related Proteins (ANPs) are mitogen‐activated protein kinase kinase kinases previously shown to have a role in immunity. In this article, we studied the in vivo intracellular dynamics of ANP1‐ and ANP3‐GFP fusions and found that under basal physiological conditions both proteins are present in the cytosol, while ANP3 is also localized in mitochondria. After elicitor perception, both proteins are present also in the plastids and nuclei, revealing a localization pattern that is so far unique. The N‐terminal region of the protein kinases is responsible for their localization in mitochondria and plastids. Moreover, we found that the localization of ANPs coincides with the sites of elicitor‐induced ROS accumulation and that plants lacking ANP function do not accumulate intracellular ROS

The intracellular ROS accumulation in elicitor-induced immunity requires the multiple organelle-targeted Arabidopsis NPK1-related protein kinases

Recognition at the plasma membrane of danger signals (elicitors) belonging to the classes of the microbe/pathogen- and damage-associated molecular patterns is a key event in pathogen sensing by plants and is associated with a rapid activation of immune responses. Different cellular compartments, including plasma membrane, chloroplasts, nuclei and mitochondria, are involved in the immune cellular program. However, how pathogen sensing is transmitted throughout the cell remains largely to be uncovered. Arabidopsis NPK1-related Proteins (ANPs) are mitogen-activated protein kinase kinase kinases previously shown to have a role in immunity. In this article, we studied the in vivo intracellular dynamics of ANP1- and ANP3-GFP fusions and found that under basal physiological conditions both proteins are present in the cytosol, while ANP3 is also localized in mitochondria. After elicitor perception, both proteins are present also in the plastids and nuclei, revealing a localization pattern that is so far unique. The N-terminal region of the protein kinases is responsible for their localization in mitochondria and plastids. Moreover, we found that the localization of ANPs coincides with the sites of elicitor-induced ROS accumulation and that plants lacking ANP function do not accumulate intracellular ROS

Subtilase-mediated biogenesis of the expanded family of SERINE RICH ENDOGENOUS PEPTIDES.

Plant signalling peptides are typically released from larger precursors by proteolytic cleavage to regulate plant growth, development and stress responses. Recent studies reported the characterization of a divergent family of Brassicaceae-specific peptides, SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs), and their perception by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2). Here, we reveal that the SCOOP family is highly expanded, containing at least 50 members in the Columbia-0 reference Arabidopsis thaliana genome. Notably, perception of these peptides is strictly MIK2-dependent. How bioactive SCOOP peptides are produced, and to what extent their perception is responsible for the multiple physiological roles associated with MIK2 are currently unclear. Using N-terminomics, we validate the N-terminal cleavage site of representative PROSCOOPs. The cleavage sites are determined by conserved motifs upstream of the minimal SCOOP bioactive epitope. We identified subtilases necessary and sufficient to process PROSCOOP peptides at conserved cleavage motifs. Mutation of these subtilases, or their recognition motifs, suppressed PROSCOOP cleavage and associated overexpression phenotypes. Furthermore, we show that higher-order mutants of these subtilases show phenotypes reminiscent of mik2 null mutant plants, consistent with impaired PROSCOOP biogenesis, and demonstrating biological relevance of SCOOP perception by MIK2. Together, this work provides insights into the molecular mechanisms underlying the functions of the recently identified SCOOP peptides and their receptor MIK2

COMPASS criteria applied to a contemporary cohort of unselected patients with stable coronary artery diseases: insights from the START registry

Aims Recently, the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial demonstrated that dual therapy reduced cardiovascular outcomes compared with aspirin alone in patients with stable atherosclerotic disease. Methods and We sought to assess the proportion of patients eligible for the COMPASS trial and to compare the epidemiology results and outcome of these patients with those without COMPASS inclusion or with any exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease. Among the 4068 patients with detailed information allowing evaluation of eligibility, 1416 (34.8%) did not fulfil the inclusion criteria (COMPASS-Not-Included), 841 (20.7%) had exclusion criteria (COMPASS-Excluded), and the remaining 1811 (44.5%) were classified as COMPASS-Like. At 1 year, the incidence of major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was 0.9% in the COMPASS-Not-Included and 2.0% in the COMPASS-Like (P = 0.01), and 5.0% in the COMPASS-Excluded group (P < 0.0001 for all comparisons). Among the COMPASS-Like population, patients with multiple COMPASS enrichment criteria presented a significant increase in the risk of MACE (from 1.0% to 3.3% in those with 1 and >_3 criteria, respectively; P = 0.012), and a modest absolute increase in major bleeding risk (from 0.2% to 0.4%, respectively; P = 0.46). Conclusion In a contemporary real-world cohort registry of stable coronary artery disease, most patients resulted as eligible for the COMPASS. These patients presented a considerable annual risk of MACE that consistently increases in the presence of multiple risk factors

Clinical outcomes, pharmacological treatment, and quality of life of patients with stable coronary artery diseases managed by cardiologists: 1-year results of the START study

Aims: We evaluated the 1-year clinical events, pharmacological management, and quality of life in a contemporary cohort of stable coronary artery disease (CAD) patients managed by cardiologists. Methods and results: START (STable Coronary Artery Diseases RegisTry) was a prospective, observational, nationwide study that enrolled 5070 stable CAD patients over 3 months in 183 cardiology centres in Italy. At 1 year, 4790 (94.5%) patients had data on vital status. Death occurred in 107 (2.2%) patients and the cause of death was cardiovascular in 41 (38.3%) of cases. Among the 4775 patients with follow-up data on clinical events available, a hospitalization due to cardiovascular and non-cardiovascular causes occurred in 523 (11.0%) and in 231 (4.8%) of cases, respectively. Over 60% of patients reported as 'no problems' in all domains (61.4-84.5%) of the EuroQoL quality of life 5D-5L questionnaire. Among the 3239 patients with clinical visit/telephone interview at follow-up, in whom optimal medical therapy (OMT; aspirin or thienopyridine, β-blocker, and statin) was prescribed at enrolment, 2971 (91.7%) were still receiving OMT at follow-up. At multivariable analysis, only increasing age (odds ratio 0.98; 95% confidence interval 0.97-0.99; P = 0.04) resulted as independent negative predictor of OMT persistence at 1 year from enrolment. Conclusion: In this large, contemporary registry, stable CAD patients managed by cardiologists presented a high rate of clinical events at 1 year. Nevertheless, the persistence to OMT and quality of life appeared reasonable

Prevalence and predictive role of hypertriglyceridemia in statin-treated patients at very high risk: Insights from the START study

Background and aim: Elevated triglyceride (TG) levels seem to identify subjects at increased cardiovascular risk, independent of LDL-C levels. We sought to evaluate the predictive role of hypertriglyceridemia, defined as TG levels ≥150 mg/dl, in very high risk (VHR) patients with chronic coronary syndromes (CCS) treated with statins. Methods and results: Using the data from the STable Coronary Artery Diseases RegisTry (START) study, an Italian nationwide registry, we assessed the association between the TG levels and baseline clinical characteristics, pharmacological treatment and major adverse cardio-cerebrovascular events (MACCE) at 1 year in a large cohort of statin-treated patients at VHR. Of the 4751 consecutive patients with CCS enrolled in the registry and classified as VHR, 2652 (55.8%) had TG values available (mean 120.6 ± 54.9) and were treated with at least a statin at baseline: 2019 (76.1%) with TG < 150 and 633 (23.9%) with TG ≥ 150 mg/dl. At 1 year from enrolment, MACCE occurred in 168 (6.3%) patients, without differences between the two groups of TG (5.9 vs 7.6%; p = 0.14). At multivariable analysis, hypertriglyceridemia did not result as independent predictor of the MACCE (hazard ratio: 1.16; 95% confidence intervals: 0.82–1.64; p = 0.42). Conclusions: In the present large, nationwide cohort of consecutive CCS patients at VHR with statin-controlled LDL-C levels, hypertriglyceridemia was present in around 24% of cases and did not result as predictor of MACCE at 1 year. Further studies with a longer follow-up and larger sample size are needed to better define the prognostic role of TG levels when intensive LDL lowering therapies are used